JPWO2019031477A1 - Medical device and manufacturing method thereof - Google Patents

Abstract

A medical device comprising a base material and a hydrophilic polymer layer on at least a part of the base material and satisfying the following conditions (a) to (d): (a) constituting the hydrophilic polymer layer Is a hydrophilic polymer containing an acidic group; (b) the thickness of the hydrophilic polymer layer is 1 nm or more and less than 100 nm; (c) the basic group/acidic group number ratio of the hydrophilic polymer layer. Is 0.2 or less; (d) The liquid film retention time after 40 minutes of immersion in a phosphate buffer solution and ultrasonic cleaning is 15 seconds or more. Provided is a medical device in which the surface of a base material is made hydrophilic, and a method for producing the medical device by a simple method.

Description

The present invention relates to a medical device having a hydrophilic surface and a manufacturing method thereof.

2. Description of the Related Art Conventionally, in various fields, a device using a resin soft material such as silicone rubber or hydrogel, and a device using a hard material such as metal or glass have been used for various purposes. Applications of devices using soft materials include medical devices that are introduced into the living body or that cover the surface of the living body, biotechnology devices such as cell culture sheets, scaffold materials for tissue regeneration, facial packs, etc. Beauty devices. Examples of applications of the device using a hard material include electrical appliances such as personal computers, mobile phones and displays, ampoules used for injectable drugs, capillaries, biosensing chips, and other diagnostic/analytical tools.

When various devices are used, for example, as a medical device introduced into a living body or attached to a living body surface, it is important to modify the surface of the base material of the medical device for the purpose of improving biocompatibility. Become. If the surface modification can give the medical device better characteristics than those before the surface modification, such as hydrophilicity, slipperiness, and biocompatibility, the user (patient, etc.) can improve the feeling of use. It can be expected to reduce discomfort.

Various methods are known for modifying the surface of a substrate of a medical device.

In the prior art, it has been difficult to impart sufficient hydrophilicity with one kind of polymer material, and therefore a method of coating and laminating layers of two or more kinds of polymer materials one by one is known (for example, patents). Reference 1). Above all, a method of laminating two or more kinds of polymer materials one by one on a layer having a charge opposite to that of a lower layer and coating layers having different charges alternately is a LbL method (Layer by method). Layer method) and the like. In coatings obtained by such LbL methods, it is believed that each layer of substrate and polymeric material is bonded to other layers by electrostatic interaction.

Further, a method is known in which two or more kinds of polymer materials are cross-linked to a base material to coat a base material with a polymer layer having a thickness of 0.1 μm or more (see, for example, Patent Document 2).

Recently, in order to improve cost efficiency, as an improved method of the LbL method, a polyionic substance and a hydrolyzed substance during autoclave are used, and the polyionic substance is adsorbed on the surface of the silicone hydrogel by one heat treatment, and at the same time, the silicone hydrogel is adsorbed. A method of making the surface hydrophilic has been disclosed (see Patent Document 3).

Further, a method of crosslinking two kinds of hydrophilic polymers on the surface of the silicone hydrogel by one heat treatment is disclosed (see Patent Document 4).

Further, surface coating of contact lenses with an ionic polymer is disclosed (see Patent Documents 5 to 7).

Further, a surface coating of a medical device has been disclosed in which a wetting agent is used to improve wettability without adding a coupling agent (see Patent Document 8).

International Publication No. 2013/024799 Japanese Patent Publication No. 2013-533517 Japanese Patent Publication No. 2010-508563 Japanese Patent Publication No. 2014-533381 Japanese Patent Laid-Open No. 54-116947 JP-A-63-246718 JP, 2002-047365, A Japanese Patent Publication No. 2003-535626

However, in the conventional LbL coating as described in Patent Document 1, it is usual to stack multiple layers such as about 3 to 20 layers. Since many manufacturing steps are required to stack the multiple layers, there is a risk of increasing manufacturing costs. Further, when the LbL coating was examined, a problem was found in durability.

In the coating using cross-linking as described in Patent Document 2, since the thickness of the cross-linked polymer layer is 0.1 μm or more, the thickness of the polymer layer when used in a medical device such as an ophthalmic lens, for example. If is not strictly controlled, there is a problem that the refraction of light for focusing on the retina is disturbed and a poor visibility is likely to occur. Further, strict control of the thickness of the polymer layer is required, and a complicated process for crosslinking the polymer with the base material is required, which may increase the manufacturing cost.

In the improved LbL coating, as described in US Pat. No. 6,037,697, applicable substrates are limited to hydrous hydrogels. Furthermore, when the improved LbL coating was examined, the performance such as hydrophilicity of the surface was insufficient.

Regarding the method of crosslinking two kinds of hydrophilic polymers on the surface of the silicone hydrogel by one heat treatment as described in Patent Document 4, applicable substrates are limited to hydrous hydrogel. Further, the method as described in Patent Document 4 requires a step of crosslinking the carboxyl group-containing polymer with the surface of the silicone hydrogel before the heat treatment. Further, the hydrophilic polymer is cross-linked to the lens surface via a covalent bond between the epoxy group of the cross-linkable hydrophilic polymer material and the carboxyl group cross-linked to the surface of the silicone hydrogel. This cross-linking is done in aqueous solution. Since such a complicated process is required, the manufacturing cost may be increased.

In surface coating of a contact lens with an ionic polymer as described in Patent Documents 5 to 7, performance such as hydrophilicity of the surface was still insufficient.

In the surface coating of the medical device described in Patent Document 8,
Performance such as surface hydrophilicity was still insufficient.

The present invention has been made in view of the above problems of the conventional technology. That is, an object of the present invention is to provide a medical device having a hydrophilic surface and excellent durability, and a method for easily producing the medical device.

In order to achieve the above object, the present invention has the following configurations.

The present invention relates to a medical device comprising a base material and a hydrophilic polymer layer on at least a part of the base material, and satisfying the following (a) to (d).
(A) the polymer constituting the hydrophilic polymer layer is a hydrophilic polymer containing an acidic group;
(B) the thickness of the hydrophilic polymer layer is 1 nm or more and less than 100 nm;
(C) The number ratio of basic groups/acidic groups of the hydrophilic polymer layer is 0.2 or less;
(D) The liquid film holding time after 40 minutes of immersion in a phosphate buffer solution and ultrasonic cleaning is 15 seconds or more. Further, according to the present invention, the substrate is maintained at an initial stage of 2.0 or more and 6.0 or less. It is a manufacturing method of a medical device including a process of placing in a solution having pH and heating the solution, wherein the solution contains the hydrophilic polymer and an acid.

According to the present invention, unlike the prior art, it is possible to obtain a medical device having hydrophilicity on the surface and excellent in durability. Also, applicable substrates are not limited to hydrous hydrogels and silicone hydrogels. In addition, these medical devices can be obtained by a simple method.

The present invention relates to a medical device comprising a substrate and a hydrophilic polymer layer on at least a part of the substrate, and satisfying the following (a) to (d).
(A) the polymer constituting the hydrophilic polymer layer is a hydrophilic polymer containing an acidic group;
(B) the thickness of the hydrophilic polymer layer is 1 nm or more and less than 100 nm;
(C) The number ratio of basic groups/acidic groups of the hydrophilic polymer layer is 0.2 or less;
(D) The liquid film retention time after 40 minutes of immersion in a phosphate buffer solution and ultrasonic cleaning is 15 seconds or more. The medical device of the present invention may have a lens shape, and is a ophthalmic lens. It is preferable to have. Specific examples include ophthalmic lenses such as contact lenses, intraocular lenses, artificial corneas, corneal inlays, corneal onlays, and spectacle lenses. Ophthalmic lenses, especially contact lenses, are among the most preferred embodiments of the present invention.

The medical device of the present invention may have a tubular shape. Examples of tubular devices include infusion tubes, gas transport tubes, drainage tubes, blood circuits, coating tubes, catheters, stents, sheaths, tube connectors, access ports and the like.

The medical device of the present invention may have a sheet shape or a film shape. Specific examples thereof include a skin covering material, a wound covering material, a skin protecting material, a skin drug carrier, a biosensor chip, and an endoscope covering material.

The medical device of the present invention may have a storage container shape. Specific examples include drug carriers, cuffs, drainage bags and the like.

Ophthalmic lenses, especially contact lenses, are among the most preferred embodiments of the present invention.

In the present invention, both a hydrous substrate and a non-hydrous substrate can be used as the substrate of the medical device. Examples of the material of the water-containing substrate include hydrogel and silicone hydrogel. Silicone hydrogels are particularly preferred because of their flexibility and the high oxygen permeability which gives them excellent wearing comfort. Examples of the non-hydrous base material include a low hydrous soft material and a low hydrous hard material.

The present invention can be applied to a general hydrogel containing no silicone and a hydrogel containing silicone (hereinafter referred to as silicone hydrogel) as to the material of the water-containing substrate. Since it can greatly improve the surface properties, it can be particularly preferably used for silicone hydrogel.

Hereinafter, United States Adapted Names (USAN) may be used to represent a material. In USAN, a variety of materials may be represented by adding symbols such as A, B, and C to the end, but in the present specification, all variants are represented when the last symbol is not given. For example, when simply expressed as “ocufilcon”, all the variants of ocufilcon such as “ocufilconA”, “ocufilconB”, “ocufilconC”, “ocufilconD”, “ocufilconE”, “ocufilconF”, etc. are represented.

As a specific example of the hydrogel, for example, when the hydrogel is a contact lens, a hydrogel selected from the group belonging to the contact lens classifications Group 1 to Group 4 defined by the US Food and Drug Administration (FDA) is preferable. Group2 and Group4 are more preferable, and Group4 is particularly preferable, because they show good water wettability and antifouling property.

Group1 represents a non-ionic hydrogel lens with a water content of less than 50% by weight. Specific examples include tefilcon, tetrafilcon, helfilcon, mafilcon, polymacon, and thioxifilcon.

Group 2 is a nonionic hydrogel lens having a water content of 50% by mass or more. Specific examples include alfafilcon, omafilcon, hioxifilcon, nelfilcon, nesofilcon, hilafilcon and acofilcon. Omafilcon, hioxifilcon, nelfilcon, and nesofilcon are more preferable because they show good water-wettability and antifouling property, and omafilcon and hioxifilcon are more preferable, and omafilcon is particularly preferable.

Group 3 represents an ionic hydrogel lens with a water content of less than 50% by weight. Specifically, deltafilcon etc. are mentioned.

Group 4 is an ionic hydrogel lens having a water content of 50% by mass or more. Specific examples thereof include etafilcon, focofilcon, ocufilcon, chemfilcon, methafilcon, and vilfilcon. Etafilcon, focofilcon, ocufilcon, and chemfilcon are more preferable, and etafilcon and ocufilcon are more preferable, and etafilcon are particularly preferable, because they exhibit good water wettability and antifouling property.

Further, as a specific example of the silicone hydrogel, for example, when the silicone hydrogel is a contact lens, a silicone hydrogel selected from the group belonging to the contact lens group Group 5 defined by the US Food and Drug Administration (FDA) is preferable.

The silicone hydrogel is preferably a polymer having a silicon atom in the main chain and/or side chain and having hydrophilicity, and examples thereof include a copolymer of a monomer having a siloxane bond and a hydrophilic monomer.

Specific examples thereof include lotrafilcon, galyfilcon, narafilcon, senofilcon, comfilcon, enfilcon, balafilcon, efrofilcon, fanfilcon, somofilcon, samfilcon, olifilcon, asmofilcon, formofilcon, stenfilcon, abafilcon, mangofilcon, riofilcon, sifilcon, such larafilcon and delefilcon is .. From the fact that they exhibit good wettability and slipperiness, lotrafilcon, gallyfilcon, narafilcon, senofilcon, comfilcon, enfilcon, stenfilcon, somofilcon, delefilcon, balafilcon, seleconon, balafilcon, sol, more preferred. Preferred are narafilcon, senofilcon and comfilcon.

As the low hydrous soft material and the low hydrous hard material, for example, when used in a medical device such as an ophthalmic lens, since it exhibits high oxygen permeability capable of supplying sufficient oxygen to the cornea, a silicon atom is used. It is preferable that the material includes.

As a specific example of the low hydrous hard material, for example, when the low hydrous hard material is a contact lens, a low hydrous hard material selected from the group belonging to the category of contact lenses defined by the US Food and Drug Administration (FDA) is preferable.

As such a low hydrous hard material, a polymer containing a silicon atom in its main chain and/or side chain is preferable. For example, it is a molded product containing a polymer containing a siloxane bond as a main component. Among these polymers containing a silicon atom, those containing a silicon atom in the polymer through a siloxane bond are preferable from the viewpoint of oxygen permeability. Specific examples of such a polymer include tris(trimethylsiloxy)silylpropyl methacrylate, polydimethylsiloxane having a double bond at both ends, a homopolymer using a silicone-containing (meth)acrylate, or a monomer thereof and another monomer. Examples thereof include copolymers with monomers.

Specific examples thereof include neofocon, pasifocon, telefocon, silafocon, paflufocon, petrafocon and fluorofocon. Neofocon, pasifocon, telefocon, and silafocon are more preferable, neofocon, pasifocon, and telefocon are more preferable, and neofocon is particularly preferable, because they show good water wettability and antifouling property.

When the medical device of the present invention is an embodiment other than a contact lens, suitable as a low hydrous hard material is polyethylene, polypropylene, polysulfone, polyetherimide, polystyrene, polymethylmethacrylate, polyamide, polyester, epoxy resin, polyurethane. , Polyvinyl chloride and the like. Polysulfone, polystyrene, and polymethylmethacrylate are more preferable, and polymethylmethacrylate is particularly preferable, because they show good water wettability and antifouling property.

Specific examples of the low hydrous soft material include, for example, a water content of 10% by mass or less, an elastic modulus of 100 kPa or more and 2,000 kPa or less, and a tensile elongation of 50% as described in WO 2013/024799. The low hydrous soft material used for the medical devices above 3,000% is mentioned. Elastofilcon is also suitable.

When the medical device of the present invention is an embodiment other than the ophthalmic lens, suitable examples of the low hydrous soft material include silicone elastomer, soft polyurethane, polyvinyl acetate, ethylene-vinyl acetate copolymer, soft polyester resin, and soft Examples include acrylic resin, soft polyvinyl chloride, natural rubber, and various synthetic rubbers.

According to the present invention, it is possible to impart appropriate hydrophilicity and slipperiness to the surface of a medical device regardless of whether the base material is hydrous or low in water content. Therefore, the water content of the substrate may be 0 to 99% by mass. Since the effect of imparting appropriate hydrophilicity and slipperiness to the surface of the medical device is much higher, the water content of the base material is preferably 0.0001% by mass or more, and particularly preferably 0.001% by mass or more. The water content of the base material is preferably 60% by mass or less, more preferably 50% by mass or less, and further preferably 40% by mass or less.

When the medical device is a contact lens, the water content of the base material is preferably 15% by mass or more, and more preferably 20% by mass or more, because the movement of the lens in the eye is easily secured.

According to the present invention, at least a part of the surface of the medical device is rendered hydrophilic by having the hydrophilic polymer layer on at least a part of the substrate. The substrate having a hydrophilic polymer layer means that the hydrophilic polymer is formed as a layer on the surface of the substrate. A part of the hydrophilic polymer layer may enter the inside of the substrate.

The material constituting the hydrophilic polymer layer is usually a material different from the base material. However, the same material as that of the base material may be used as long as a predetermined effect can be obtained.

The polymer forming the hydrophilic polymer layer is composed of a material having hydrophilicity. However, other additives may be included as long as the hydrophilicity is not impaired. Here, the hydrophilic material is a material that is soluble in 0.0001 parts by mass or more in 100 parts by mass of water at room temperature (20 to 23° C.), and is soluble in 0.01 parts by mass or more in 100 parts by mass of water. Is more preferable, even more preferably 0.1 parts by mass or more, and particularly preferably 1 part by mass or more.

As the polymer forming the hydrophilic polymer layer, a hydrophilic polymer containing an acidic group is used. A hydrophilic polymer containing an acidic group is preferable because it can form a surface excellent in antifouling property against body fluids as well as water wettability. As the acidic group, specifically, a group selected from a carboxy group and a sulfonic acid group is preferable, and a carboxy group is particularly preferable. The carboxy group or sulfonic acid group may be a salt.

Examples of the hydrophilic polymer containing an acidic group are polymethacrylic acid, polyacrylic acid, poly(vinylbenzoic acid), poly(thiophen-3-acetic acid), poly(4-styrenesulfonic acid), polyvinylsulfonic acid, poly (2-acrylamido-2-methylpropanesulfonic acid) and salts thereof. Although the above is an example of a homopolymer, a copolymer of hydrophilic monomers composing the hydrophilic polymer or a copolymer of the hydrophilic monomer and another monomer can be preferably used.

When the hydrophilic polymer having an acidic group is a copolymer, the hydrophilic monomer having an acidic group constituting the copolymer may be an allyl group, a vinyl group, and (meth) in terms of high polymerizability. A monomer having a group selected from an acryloyl group is preferable, and a monomer having a (meth)acryloyl group is particularly preferable. Suitable examples of such a monomer include (meth)acrylic acid, vinylbenzoic acid, styrenesulfonic acid, vinylsulfonic acid, 2-acrylamido-2-methylpropanesulfonic acid, and salts thereof. .. Among these, a monomer selected from (meth)acrylic acid, 2-acrylamido-2-methylpropanesulfonic acid, and salts thereof is more preferable, and (meth)acrylic acid and salts thereof are particularly preferable. It is a monomer.

The hydrophilic polymer containing an acidic group preferably has an amide group in addition to the acidic group. In the case where the hydrophilic polymer has an amide group in addition to the acidic group, when the hydrophilic polymer dissolves in water, it exhibits an appropriate viscosity, so that not only the wettability with water but also a slippery surface can be formed.

Examples of hydrophilic polymers having an acidic group and an amide group include polyamides having a carboxyl group and copolymers of the hydrophilic monomer having an acidic group and a monomer having an amide group.

Preferable examples of polyamides having a carboxyl group include polyamino acids such as polyaspartic acid and polyglutamic acid, and polypeptides.

The monomer having an amide group is preferably a monomer selected from a monomer having a (meth)acrylamide group and an N-vinylcarboxylic acid amide (including a cyclic one) from the viewpoint of ease of polymerization. Preferable examples of such a monomer include N-vinylpyrrolidone, N-vinylcaprolactam, N-vinylacetamide, N-methyl-N-vinylacetamide, N-vinylformamide, N,N-dimethylacrylamide, N,N-diethyl. Mention may be made of acrylamide, N-isopropylacrylamide, N-(2-hydroxyethyl)acrylamide, acryloylmorpholine and acrylamide. Among these, N-vinylpyrrolidone, N,N-dimethylacrylamide and N,N-diethylacrylamide are preferable in terms of slipperiness, and N,N-dimethylacrylamide is particularly preferable.

Specific preferred examples of the copolymer of a hydrophilic monomer having an acidic group and a monomer having an amide group include (meth)acrylic acid/N-vinylpyrrolidone copolymer, (meth)acrylic acid/N,N-dimethylacrylamide. Copolymer, (meth)acrylic acid/N,N-diethylacrylamide copolymer, 2-acrylamido-2-methylpropanesulfonic acid/N-vinylpyrrolidone copolymer, 2-acrylamido-2-methylpropanesulfonic acid/ N,N-dimethylacrylamide copolymer and 2-acrylamido-2-methylpropanesulfonic acid/N,N-diethylacrylamide copolymer. Particularly preferred is a (meth)acrylic acid/N,N-dimethylacrylamide copolymer.

When a copolymer of a hydrophilic monomer having an acidic group and a monomer having an amide group is used, the copolymerization ratio is such that [mass of hydrophilic monomer having acidic group]/[mass of monomer having amide group] is 1 It is preferably /99 to 99/1. The copolymerization ratio of the hydrophilic monomer having an acidic group is more preferably 2% by mass or more, further preferably 5% by mass or more, more preferably 7% by mass or more, still more preferably 10% by mass or more. The copolymerization ratio of the hydrophilic monomer having an acidic group is more preferably 90% by mass or less, further preferably 80% by mass or less, and further preferably 70% by mass or less. The copolymerization ratio of the amide group-containing monomer is more preferably 10% by mass or more, further preferably 20% by mass or more, still more preferably 30% by mass or more. Further, the copolymerization ratio of the monomer having an amide group is more preferably 98% by mass or less, further preferably 95% by mass or less, further preferably 93% by mass or less, and further preferably 90% by mass or less. When the copolymerization ratio of the hydrophilic monomer having an acidic group and the monomer having an amide group is in the above range, functions such as slipperiness and antifouling property against body fluid are easily exhibited.

In addition, it is possible to copolymerize the hydrophilic monomer having an acidic group and the monomer having an amide group with one or more monomers having different acidic groups or amide groups or a monomer having no acidic group or amide group. is there.

Suitable examples of monomers other than the above include hydroxyethyl (meth)acrylate, hydroxypropyl (meth)acrylate, hydroxybutyl (meth)acrylate, hydroxyethyl (meth)acrylamide, (meth)acrylamide, glycerol (meth)acrylate, Examples thereof include caprolactone-modified 2-hydroxyethyl (meth)acrylate, N-(4-hydroxyphenyl)maleimide, hydroxystyrene, vinyl alcohol (carboxylic acid vinyl ester as a precursor). Among these, a monomer having a (meth)acryloyl group is preferable, and a (meth)acrylic acid ester monomer is more preferable, from the viewpoint of ease of polymerization. From the viewpoint of improving antifouling property against body fluid, hydroxyethyl (meth)acrylate, hydroxypropyl (meth)acrylate, and glycerol (meth)acrylate are preferable, and hydroxyethyl (meth)acrylate is particularly preferable. It is also possible to use a monomer that exhibits functions such as hydrophilicity, antibacterial properties, antifouling properties, and drug efficacy.

When copolymerizing a hydrophilic monomer having an acidic group and a monomer having an amide group with a monomer having a different acidic group or amide group or a third monomer component which is a monomer having no acidic group or amide group The copolymerization ratio of the third monomer component is more preferably 2% by mass or more, further preferably 5% by mass or more, still more preferably 10% by mass or more. The copolymerization ratio of the third monomer component is more preferably 90% by mass or less, further preferably 80% by mass or less, and even more preferably 70% by mass or less.

When the copolymerization ratio of the monomer having an acidic group, the monomer having an amide group, and the third monomer component is within the above range, functions such as slipperiness and antifouling property against body fluid are easily exhibited.

Further, additives and the like other than the above materials may be contained in the hydrophilic polymer layer as long as the characteristics required for the medical device are not impaired. Furthermore, the hydrophilic polymer layer may contain one or more kinds of other hydrophilic polymers in addition to the hydrophilic polymer containing an acidic group. However, since the manufacturing method tends to be complicated, it is preferable that the hydrophilic polymer layer is composed of only a hydrophilic polymer containing one kind of acidic group.

Here, one type of polymer means a polymer or a group of polymers (isomers, complexes, etc.) produced by one synthetic reaction. When a plurality of monomers are used to form a copolymer, even if the constituent monomer species are the same, the polymers synthesized with different blending ratios are not said to be the same.

Further, the hydrophilic polymer layer is composed of only one kind of hydrophilic polymer containing an acidic group means that the hydrophilic polymer layer does not contain any polymer other than the hydrophilic polymer having the acidic group, or if other than that. Even if the above polymer is included, it means that the content of the other polymer is preferably 3 parts by mass or less with respect to 100 parts by mass of the hydrophilic polymer having the acidic group. The content of the other polymer is more preferably 0.1 part by mass or less, further preferably 0.0001 part by mass or less.

Even if the other polymer is a basic polymer, if the content is within the above range, it is possible to suppress a problem in transparency. In the prior art, an acidic polymer and a basic polymer were used in combination because a hydrophilic polymer is laminated on the surface of a base material by utilizing the electrostatic adsorption effect, but according to the present invention, only one type of polymer is used. It is also possible to form a hydrophilic polymer layer consisting of on the surface of the substrate.

When the hydrophilic polymer layer contains a basic group, the number ratio of basic group/acidic group is preferably 0.2 or less. Since the salt derived from the reaction of the acidic group and the basic group is not formed and the transparency is excellent, the ratio is more preferably 0.1 or less, further preferably 0.05 or less. Here, the basic group means a basic functional group, and examples thereof include an amino group and a salt thereof.

In the present invention, the hydrophilic polymer having an acidic group constituting the hydrophilic polymer layer is one kind selected from at least a part of the surface of the base material, selected from hydrogen bond, ionic bond, van der Waals bond, hydrophobic bond and complex formation. The above chemical bond is formed. Here, the hydrophilic polymer layer may be bound to the base material by a covalent bond, but since it can be produced by a simple process, the hydrophilic polymer layer is rather bound to the base material by a covalent bond. It is preferable not to have it.

The medical device of the present invention preferably has a hydrophilic polymer layer on the entire surface of one surface of the substrate, depending on the application. When the substrate has no thickness, or has a two-dimensional shape that is negligible even if there is a thickness, it is preferable that the hydrophilic polymer layer be present on the entire one surface of the substrate surface. It is also preferable that the hydrophilic polymer layer is present on the entire surface of the substrate.

In addition, since the hydrophilic polymer can be produced in a simple process regardless of whether the substrate is hydrous or non-hydrous, a covalent bond is formed between the hydrophilic polymer and the substrate. It is preferable not to have it. Having no covalent bond is judged by not containing a chemically reactive group. Specific examples of the chemically reactive group include, but are not limited to, an azetidinium group, an epoxy group, an isocyanate group, an aziridine group, an azlactone group, and combinations thereof.

The thickness of the hydrophilic polymer layer is 1 nm or more and less than 100 nm when the cross section of the device in a dry state is observed using a transmission electron microscope. When the thickness is in this range, functions such as wettability and slipperiness are likely to be exhibited. The thickness is more preferably 5 nm or more, further preferably 10 nm or more. The thickness is more preferably 95 nm or less, further preferably 90 nm or less, and particularly preferably 85 nm or less. When the thickness of the hydrophilic polymer layer is less than 100 nm, it is excellent in water wettability and slipperiness, and when used in a medical device such as an ophthalmic lens, the refraction of light for focusing on the retina is not disturbed and the visibility is poor. Is less likely to occur.

The thickness of the hydrophilic polymer layer is 1 nm or more and less than 100 nm when observing a device cross section in a frozen state in a water-containing state (hereinafter, frozen state) with a scanning transmission electron microscope. It is preferable because functions such as wettability and slipperiness are easily exhibited. The thickness is more preferably 5 nm or more, further preferably 10 nm or more, particularly preferably 15 nm or more. The thickness is more preferably 95 nm or less, further preferably 90 nm or less, and particularly preferably 85 nm or less. The thickness of the frozen hydrophilic polymer layer can be measured by scanning transmission electron microscope observation using a cryotransfer holder.

When the thickness of the frozen hydrophilic polymer layer is 100 nm or more, for example, when it is used for a medical device such as an ophthalmic lens, refraction of light for focusing on the retina is disturbed, and poor visibility is likely to occur, which is preferable. Absent.

Further, when the medical device of the present invention is used as a contact lens, the average thickness of the hydrophilic polymer layer on the surface in contact with the eyelid side called the front curve surface, and the hydrophilic polymer layer on the surface in contact with the cornea side called the base curve surface. May be the same as the average thickness, but since the excessive movement of the contact lens during wearing is suppressed and the wearing feeling is improved, the difference in thickness between the front curve surface and the base curve surface exceeds 20%. It is preferable. The difference in average thickness is the ratio of the average thickness of the hydrophilic polymer layer to the average thickness of the thinner one to the average thickness of the thinner hydrophilic polymer layer.

When the hydrophilic polymer layer on the front curve surface is thicker, the water retention on the front curve surface in contact with air is higher and the tear fluid is less likely to evaporate, so that the dry feeling during wearing is easily suppressed.

When the hydrophilic polymer layer on the base curve surface is thicker, the base curve surface is more slippery, friction between the cornea and the base curve surface at the time of blinking is small, and the cornea is less likely to be damaged.

The average thickness can be measured by the same method as the thickness measurement of the hydrophilic polymer layer in the dry state. The film thickness is measured at 5 places for each visual field by changing 4 places, and the average of the film thicknesses at 20 places is taken as the average thickness.

The hydrophilic polymer layer is preferably in a state of being separated into two or more layers or two or more phases.

Here, the state in which the hydrophilic polymer layer is separated into two or more layers means that a multilayer structure of two or more layers is observed in the hydrophilic polymer layer when the cross section of the medical device is observed using a transmission electron microscope. Indicates the state. When it is difficult to judge the separation of layers only by observation with a transmission electron microscope, the cross section of a medical device is scanned with a transmission transmission electron microscope, electron energy loss spectroscopy, energy dispersive X-ray spectroscopy, time-of-flight secondary The determination is made by analyzing the element or composition of the cross section using a means capable of elemental analysis or composition analysis such as ion mass spectrometry.

Further, the state where the hydrophilic polymer layer is phase-separated into two or more phases means a state where the hydrophilic polymer layer is phase-separated into two or more phases when the cross section of the medical device is observed using a transmission electron microscope. The observed condition is shown. The same applies to the case where it is difficult to determine the phase separation only by observation with a transmission electron microscope.

Conventionally, two or more kinds of polymers were required to form a polymer layer having two or more layers or two or more phases on the surface of a substrate, but in the present invention, even when only one kind of polymer is present, It has been found that a hydrophilic polymer layer separated into two or more layers or two or more phases can be formed on the surface of a substrate.

When the hydrophilic polymer layer has a multilayer structure of two or more layers, the hydrophilic polymer layer becomes sufficiently thick and the wettability and slipperiness become better. Further, when the hydrophilic polymer layer has a phase-separated state of two or more phases, it becomes easy to distinguish it from minute foreign matters such as dust and dust when the cross section of the medical device is observed using a transmission electron microscope. , It is easy to confirm the polymer layer formation on the surface of the substrate, and it is efficient in quality inspection.

Further, in the hydrophilic polymer layer, it is preferable that at least a part of the hydrophilic polymer layer exists in a state of being mixed with the substrate. When the hydrophilic polymer layer is mixed with the base material, the cross section of the medical device is an element such as scanning transmission electron microscopy, electron energy loss spectroscopy, energy dispersive X-ray spectroscopy, time-of-flight secondary ion mass spectrometry, etc. It can be confirmed by observing an element derived from the substrate in at least a part of the cross-sectional structure of the substrate and the hydrophilic polymer layer before and after the formation of the hydrophilic polymer layer, when observed by an observing means capable of analysis or composition analysis. By mixing the hydrophilic polymer layer with the base material, the hydrophilic polymer can be more firmly fixed to the base material.

When at least a part of the hydrophilic polymer layer exists in a state of being mixed with the base material, "a layer in which at least a part of the hydrophilic polymer layer is mixed with the base material" (hereinafter referred to as a miscible layer) and "a layer made of a hydrophilic polymer" It is preferable to observe a two-layer structure consisting of the following (hereinafter referred to as a single layer). The thickness of the admixture layer is preferably 3% or more, more preferably 5% or more, still more preferably 10% or more, based on the total thickness of the admixture layer and the single layer. The thickness of the admixture layer is preferably 98% or less, more preferably 95% or less, even more preferably 90% or less, and particularly preferably 80% or less, based on the total thickness of the admixture layer and the single layer. If the thickness ratio of the admixture layer is too small, the admixture of the hydrophilic polymer and the substrate is not sufficient, which is not preferable. If the thickness ratio of the admixture layer is too large, the properties of the hydrophilic polymer may not be sufficiently exhibited, which is not preferable.

The number of layers or the number of phases is preferably 2 to 3 layers or 2 to 3 phases, more preferably 2 layers or 2 phases, from the viewpoint of excellent transparency of the medical device. If the medical device has high transparency, the skin condition can be easily visually observed without peeling the medical device from the skin when used as a skin material, for example. Further, if the medical device has high transparency, it can be used as an ophthalmic lens or the like.

When the medical device of the present invention is an ophthalmic device such as a medical device or an ophthalmic lens that is used by being stuck on the surface of a living body, the viewpoint of preventing sticking to the skin of the user and the cornea of the wearer From the viewpoint of preventing sticking, it is preferable that the liquid film holding time on the surface of the medical device is long.

Here, the liquid film holding time in the present invention means that the liquid film on the surface of the medical device is not broken when the medical device immersed in the phosphate buffer is pulled out of the liquid and held so that the surface becomes vertical in the air. It is time to be held in. In addition, "the liquid film is cut off" refers to a state in which a phenomenon of repelling water occurs on the surface of the medical device. The liquid film holding time is preferably 15 seconds or longer, more preferably 20 seconds or longer, and particularly preferably 25 seconds or longer.

In the prior art, when the thickness of the hydrophilic polymer layer on the surface is less than 100 nm, even a medical device having good water wettability will have extremely low water wettability when subjected to ultrasonic cleaning. The wettability tended not to recover even after being left in water at room temperature for a short time (for example, about 1 hour). Although the details of the mechanism of manifestation of such a phenomenon are unknown, the hydrophilic polymer layer on the surface is peeled off or eluted by ultrasonic waves, or the composition of the hydrophilic polymer layer surface is changed to cause hydrophobicity. It is thought that the cause is strengthening. Therefore, a medical device whose water wettability is deteriorated when it is subjected to ultrasonic cleaning is not preferable because there is a risk that the surface state is changed by an external stimulus and the water wettability is deteriorated. On the contrary, a device that does not deteriorate in water wettability even after being subjected to ultrasonic cleaning or that recovers in a short time even if it deteriorates can be said to be an excellent medical device in which the surface condition is unlikely to change due to external stimulus.

When the medical device of the present invention is an ophthalmic device such as an ophthalmic lens, a liquid film on the surface of the medical device after being subjected to ultrasonic cleaning, from the viewpoint of not feeling a dry feeling and maintaining a good wearing feeling for a long time. A long holding time is preferable.

The medical device was subjected to ultrasonic cleaning (power consumption: 40 W) in a phosphate buffer for 5 seconds, and then the liquid film retention time on the surface of the medical device after immersion in the phosphate buffer for 40 minutes at room temperature was evaluated. When the liquid film retention time on the surface of the medical device after 40 minutes is 15 seconds or more, it means that the surface of the medical device has sufficient water wettability and durability. The liquid film holding time is preferably 15 seconds or longer, more preferably 20 seconds or longer, and particularly preferably 25 seconds or longer. In particular, when the liquid film holding time is the same as that before ultrasonic cleaning, it is preferable because the durability is further improved. Details of the measuring method will be described later.

When the medical device of the present invention is an ophthalmic device such as an ophthalmic lens, it is preferable that the surface of the medical device has a low dynamic contact angle from the viewpoint of preventing sticking to the cornea of the wearer. The dynamic contact angle is preferably 60° or less, more preferably 55° or less, and particularly preferably 50° or less. The dynamic contact angle (at the time of advancing, immersion speed: 0.1 mm/sec) is measured on a sample in a wet state with a phosphate buffer. Details of the measuring method will be described later.

Further, when the medical device of the present invention is, for example, a medical device that is inserted into a living body and used, it is preferable that the surface of the medical device has excellent slipperiness. As the index showing the slipperiness, it is preferable that the friction coefficient measured by the method shown in the examples of the present specification is small. The coefficient of friction is preferably 0.7 or less, more preferably 0.5 or less, and particularly preferably 0.3 or less. Further, when the friction is extremely small, it tends to be difficult to handle when putting on and taking off, so the friction coefficient is preferably 0.001 or more, and more preferably 0.002 or more.

The tensile elastic modulus of the medical device of the present invention should be appropriately selected according to the type of the medical device, but in the case of a soft medical device such as an ophthalmic lens, the tensile elastic modulus is preferably 10 MPa or less, and 5 MPa. The following is preferred, 3 MPa or less is more preferred, 2 MPa or less is even more preferred, 1 MPa or less is even more preferred, and 0.6 MPa or less is most preferred. The tensile modulus is preferably 0.01 MPa or higher, more preferably 0.1 MPa or higher, even more preferably 0.2 MPa or higher, and most preferably 0.25 MPa or higher. In the case of a soft medical device such as an ophthalmic lens, if the tensile modulus is too small, it tends to be too soft and difficult to handle. If the tensile modulus is too large, it tends to be too hard, resulting in poor wearing and wearing feeling.

The rate of change in tensile modulus before and after the formation of the hydrophilic polymer layer of the medical device of the present invention is preferably 15% or less, more preferably 14% or less, and particularly preferably 13% or less. If the rate of change in tensile modulus is too large, it may cause deformation or poor feeling in use, which is not preferable. Details of the measuring method will be described later.

The antifouling property of the medical device of the present invention can be evaluated by the adhesion of mucin and the adhesion of lipid (methyl palmitate). The smaller the adhered amount according to these evaluations, the more excellent the feeling in use and the lower the risk of bacterial reproduction, which is preferable. Mucin adhesion amount is preferably 10 [mu] g / cm ² or less, more preferably 8 [mu] g / cm ² or less, particularly preferably 6 [mu] g / cm ² or less. Details of the measuring method will be described later.

Next, a method for manufacturing the medical device of the present invention will be described.

The method for producing a medical device of the present invention includes a step of placing a substrate in a solution having an initial pH of 2.0 or more and 6.0 or less and heating the solution, wherein the solution has the hydrophilic property. It contains a polymer and an acid.

Here, the inventors of the present invention heat the substrate in a state where the substrate is placed in a solution containing the hydrophilic polymer and an acid (preferably an organic acid) and having an initial pH of 2.0 or more and 6.0 or less. It has been found that such a very simple method can impart excellent water wettability and slipperiness to a medical device. According to this method, a hydrophilic polymer layer containing an acidic group is provided regardless of a conventionally known special method, for example, a method utilizing an electrostatic adsorption action in which an acidic polymer and a basic polymer are used in combination. From the viewpoint of shortening the manufacturing process, it is very important industrially.

The hydrophilic polymer preferably has a molecular weight of 2,000 to 1,500,000. The molecular weight is preferably 50,000 or more, more preferably 250,000 or more, and further preferably 500,000 or more, since it exhibits sufficient water wettability and slipperiness. The molecular weight is preferably 1,200,000 or less, more preferably 1,000,000 or less, and further preferably 900,000 or less. Here, as the molecular weight, a polyethylene glycol-equivalent mass average molecular weight measured by a gel permeation chromatography method (aqueous solvent) is used.

Further, regarding the concentration of the hydrophilic polymer in the solution at the time of production, if the concentration is increased, the thickness of the hydrophilic polymer layer generally obtained increases. However, if the concentration of the hydrophilic polymer is too high, it may be difficult to handle during production due to an increase in viscosity. Therefore, the concentration of the hydrophilic polymer in the solution is preferably 0.0001 to 30% by mass. The concentration of the hydrophilic polymer is more preferably 0.001% by mass or more, and further preferably 0.005% by mass or more. The concentration of the hydrophilic polymer is more preferably 20% by mass or less, further preferably 15% by mass or less.

In the above step, the initial pH range of the solution containing the hydrophilic polymer is within the range of 2.0 to 6.0 because the solution does not become turbid and a medical device having good transparency can be obtained. It is preferable to have. The initial pH is more preferably 2.1 or higher, even more preferably 2.2 or higher, even more preferably 2.4 or higher, and particularly preferably 2.5 or higher. The initial pH is more preferably 5.0 or less, further preferably 4.0 or less, and further preferably less than 3.5.

When the initial pH is 2.0 or more, the solution becomes less turbid. When the solution does not become turbid, the surface of the medical device tends to have high wettability and slipperiness, which is preferable. When the initial pH is 6.0 or less, the obtained hydrophilic polymer layer tends to be present in two or more layers or in two or more phases separately, and the wettability and the slipperiness of the surface of the medical device may be reduced. It is preferable because it does not decrease.

Since excellent water-wettability and slipperiness can be imparted to the base material, when the base material is a material containing silicon atoms, the initial pH range of the solution containing the hydrophilic polymer is 3.4. The following is preferable, 3.3 or less is more preferable, and 3.0 or less is further preferable. When the base material is a material containing no silicon atom, the initial pH range is preferably 4.0 or less, more preferably 3.5 or less, and further preferably 3.3 or less.

The pH of the above solution can be measured using a pH meter (for example, pH meter Eutech pH2700 (Eutech Instruments)). Here, the initial pH of the solution containing the hydrophilic polymer means that after all the hydrophilic polymer was added to the solution, the solution was homogenized by stirring for 2 hours at room temperature (23 to 25° C.) using a rotor. Refers to the pH value measured afterwards and before placing the substrate in solution and heating. In the present invention, the second decimal place of the pH value is rounded off.

The pH of the solution may change when a heating operation is performed. The pH of the solution after the heating operation is also preferably 2.0 to 6.0. The pH after heating is more preferably 2.1 or more, more preferably 2.2 or more, and particularly preferably 2.3 or more. Further, the pH after heating is more preferably 5.9 or less, more preferably 5.5 or less, further preferably 5.0 or less, and particularly preferably 4.8 or less. When the pH of the solution after performing the heating operation is within the above range, the pH of the solution is maintained in an appropriate condition during the heating step, and the obtained medical device has suitable physical properties. The pH can be adjusted by performing a heating operation in the present invention to modify the surface of the base material used for the medical device, and then performing a neutralization treatment or adding water. The pH of the solution after the so-called heating operation is the pH before the pH adjustment treatment.

As a solvent for the solution containing the hydrophilic polymer, water is preferably cited. The pH of the solution can be adjusted by adding acid to the solution. As such an acid, an organic acid and an inorganic acid can be used. Preferable specific examples of the organic acid include acetic acid, citric acid, formic acid, ascorbic acid, trifluoromethanesulfonic acid, methanesulfonic acid, propionic acid, butyric acid, glycolic acid, lactic acid, malic acid and the like. Specific preferred examples of the inorganic acid include nitric acid, sulfuric acid, phosphoric acid, hydrochloric acid and the like. Among these, organic acids are preferable from the viewpoints that a more excellent hydrophilic surface is easily obtained, safety to living organisms is high, and handling is easy. Organic acids having 1 to 20 carbon atoms are preferable. More preferably, an organic acid having 2 to 10 carbon atoms is further preferable. Among the organic acids, acetic acid, citric acid, formic acid, ascorbic acid, trifluoromethanesulfonic acid, methanesulfonic acid, propionic acid, butyric acid, glycolic acid, lactic acid and malic acid are preferable, and formic acid, malic acid, citric acid and ascorbic acid are preferable. More preferably, citric acid and ascorbic acid are more preferable. Among the inorganic acids, sulfuric acid is preferred from the viewpoints that it is volatile, odorless, and easy to handle.

It is also preferable to add a buffering agent to the solution because it facilitates fine adjustment of pH and makes the base material less likely to become cloudy when the base material is a material containing a hydrophobic component.

As the buffer, a known physiologically compatible buffer can be used. For example: Boric acid, borates (eg sodium borate), citric acid, citrates (eg potassium citrate), bicarbonate (eg sodium bicarbonate), phosphate buffer (eg Na ₂ HPO _{4 ).} , NaH ₂ PO ₄ and KH ₂ PO ₄ ), TRIS (tris(hydroxymethyl)aminomethane), 2-bis(2-hydroxyethyl)amino-2-(hydroxymethyl)-1,3-propanediol, bis -Amino polyol, triethanolamine, ACES (N-(2-acetamido)-2-aminoethanesulfonic acid), BES (N,N-bis(2-hydroxyethyl)-2-aminoethanesulfonic acid), HEPES( 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid), MES (2-(N-morpholino)ethanesulfonic acid), MOPS (3-[N-morpholino]-propanesulfonic acid), PIPES (piperazine- N,N'-bis(2-ethanesulfonic acid), TES (N-[tris(hydroxymethyl)methyl]-2-aminoethanesulfonic acid), and salts thereof.

The amount of buffer used is that required to be effective in achieving the desired pH. Usually, 0.001% by mass to 2% by mass, preferably 0.01% by mass to 1% by mass, more preferably 0.05% by mass to 0.30% by mass is preferably present in the solution. The range may be a combination of any of the above upper and lower limits.

Examples of the heating method include high-pressure steam sterilization method, electromagnetic wave (γ-ray, microwave, etc.) irradiation, dry heat method, flame method and the like. The high-pressure steam sterilization method is most preferable from the viewpoint of water wettability, slipperiness, and shortening of the manufacturing process. As the device, it is preferable to use an autoclave.

The heating temperature is preferably 60° C. to 200° C. from the viewpoint that a medical device surface exhibiting good water wettability and slipperiness can be obtained and the strength of the medical device itself is little affected. The heating temperature is more preferably 80°C or higher, further preferably 90°C or higher, further preferably 101°C or higher, particularly preferably 110°C or higher. The heating temperature is more preferably 180°C or lower, further preferably 170°C or lower, and particularly preferably 150°C or lower.

When the heating time is too short, it is difficult to obtain a medical device surface showing good wettability and slipperiness, and when it is too long, the strength of the medical device itself may be affected, so that the heating time is preferably 5 minutes to 600 minutes. .. The heating time is more preferably 10 minutes or longer and more preferably 15 minutes or longer. Further, the heating time is more preferably 400 minutes or less, and more preferably 300 minutes or less.

After the above heat treatment, the obtained medical device may be further subjected to other treatment. As other treatment, a method of performing the same heat treatment again in a solution containing a hydrophilic polymer, a method of performing a similar heat treatment by replacing the solution with a solution containing no hydrophilic polymer, a method of performing radiation irradiation, Examples thereof include a method of performing LbL treatment (Layer by Layer treatment) in which polymer materials having opposite charges are alternately coated one by one, a method of performing a crosslinking treatment with a metal ion, and a method of performing a chemical crosslinking treatment.

Moreover, you may perform a pretreatment to a base material before the said heat processing. Examples of the pretreatment include hydrolysis treatment with an acid such as polyacrylic acid and an alkali such as sodium hydroxide.

However, in light of the idea of the present invention that makes the surface of the substrate hydrophilic by a simple method, it is preferable to carry out the treatment within a range that does not make the manufacturing process too complicated.

As the radiation used for the above-mentioned radiation irradiation, various ion rays, electron rays, positron rays, X-rays, γ rays and neutron rays are preferable, more preferable are electron rays and γ rays, and most preferable are γ rays.

As the above LbL treatment, it is preferable to use a treatment using an acidic polymer and a basic polymer as described in, for example, WO 2013/024800.

As the metal ion used for the crosslinking treatment with the above metal ion, various metal ions are preferable, more preferably monovalent and divalent metal ions, and most preferably divalent metal ion. Alternatively, a chelate complex may be used.

As the above-mentioned chemical crosslinking treatment, for example, a reaction between an epoxy group and a carboxyl group as described in JP-A-2014-533381 or a known acidic hydrophilic polymer having a hydroxyl group is formed. It is preferable to use a crosslinking treatment.

In the method in which the above solution is replaced with a solution containing no hydrophilic polymer and the same heat treatment is carried out, the solution containing no hydrophilic polymer is not particularly limited, but a buffer solution is preferable. As the buffer, the above-mentioned one can be used.

The pH of the buffer solution is preferably in the physiologically acceptable range of 6.3 to 7.8. The pH of the buffer solution is preferably 6.5 or higher, more preferably 6.8 or higher. Further, the pH of the buffer solution is preferably 7.6 or less, more preferably 7.4 or less.

In the manufacturing method of the present invention, it is preferable that the amount of change between the medical device obtained after the end of the heating step and the water content of the base material before the start of the heating step is 10 percentage points or less. Here, the amount of change in water content (percentage points) is the difference between the water content (mass %) of the obtained medical device and the water content (mass %) of the base material as the raw material.

The amount of change in the water content of the medical device before and after the formation of the hydrophilic polymer layer is, for example, when used in an ophthalmic device such as an ophthalmic lens, from the viewpoint of preventing poor visibility and deformation caused by the distortion of the refractive index due to the improved water content. Therefore, 10 percentage points or less are preferable, 8 percentage points or less are more preferable, and 6 percentage points or less are particularly preferable. Details of the measuring method will be described later.

In addition, the rate of change in size of the medical device before and after the formation of the hydrophilic polymer layer is preferably 5% or less, and more preferably 4 or less when used in an ophthalmic device such as an ophthalmic lens from the viewpoint of preventing corneal damage due to deformation. It is preferably 3% or less, and particularly preferably 3% or less. Details of the measuring method will be described later.

Hereinafter, the present invention will be specifically described with reference to Examples, but the present invention is not limited thereto. First, an analysis method and an evaluation method will be shown.

<Water wettability (liquid film retention time)>
The medical device was left to stand in a storage container at room temperature for 24 hours or more. For the evaluation of only the commercially available contact lens described in the comparative example, the sample was lightly washed in 50 mL of a phosphate buffer solution in a beaker at room temperature, and then left still in 50 mL of a fresh phosphate buffer solution for 24 hours or more.

The medical device was pulled up from the phosphate buffer solution that had been immersed in the static state, and the time for which the liquid film on the surface was retained when it was retained in the air was visually observed, and the average value of N=3 was determined according to the following criteria.
A: The liquid film on the surface is retained for 20 seconds or more.
B: The liquid film on the surface breaks in 15 seconds or more and less than 20 seconds.
C: The liquid film on the surface breaks in 5 seconds or more and less than 15 seconds.
D: The liquid film on the surface breaks in 1 second or more and less than 5 seconds.
E: The liquid film on the surface is cut off instantly (less than 1 second).

<Water wettability 40 minutes after ultrasonic cleaning (liquid film retention time)>
The medical device was left to stand in a storage container at room temperature for 24 hours or more. A new phosphate buffer solution (50 mL) was placed in a polymethylpentene beaker (volume: 100 mL), and the medical device was immersed therein. Water is put into a tank of an ultrasonic cleaner (model VS-25, manufactured by Vervoclear Co., Ltd., power consumption 40W) until the height is about 3 cm, and the phosphate buffer solution and the medical device are put therein. A beaker made of polymethylpentene was placed and ultrasonic waves were applied for 5 seconds. Then, the medical device was immediately returned to the storage container and left standing at room temperature for 40 minutes. After that, when the medical device was pulled up from the phosphate buffer and was held in the air, the time for which the liquid film on the surface was held was visually observed, and the average of N=3 (where N means the number of test samples). The value was judged according to the following criteria.
A: The liquid film on the surface is retained for 20 seconds or more.
B: The liquid film on the surface breaks in 15 seconds or more and less than 20 seconds.
C: The liquid film on the surface breaks in 5 seconds or more and less than 15 seconds.
D: The liquid film on the surface breaks in 1 second or more and less than 5 seconds.
E: The liquid film on the surface is cut off instantly (less than 1 second).

<Sliding property>
The medical device was left to stand in a storage container at room temperature for 24 hours or more. For the evaluation of only the commercially available contact lens described in the comparative example, the sample was lightly washed in 50 mL of phosphate buffer solution in a beaker at room temperature, and then left still in 50 mL of fresh phosphate buffer solution for 24 hours or more.

The medical device was taken out from the phosphate buffer solution that had been immersed in the static state, and the sensitivity was evaluated when the medical device was rubbed 5 times with a human finger (N=1).
A: It has very good slipperiness (a finger slips like flowing on the surface of a medical device and does not feel any resistance).
B: It has a slipperiness that is intermediate between A and C.
C: Medium slipperiness (finger slides on the surface of the medical device and hardly feels resistance).
D: Almost no slipperiness (middle level between C and E).
E: No slipperiness (finger does not easily slide on the surface of the medical device and feels great resistance).

<Water content of base material and medical device>
The substrate was immersed in a phosphate buffer solution and allowed to stand at room temperature for 24 hours or longer. After pulling up the substrate from the phosphate buffer and wiping the surface moisture with a wiping cloth (“Kimwipe” (registered trademark) made by Nippon Paper Crecia), the mass (Ww) of the substrate was measured. Then, the substrate was dried with a vacuum dryer at 40° C. for 2 hours, and then the mass (Wd) was measured. From these masses, the water content of the substrate was calculated by the following formula (1). When the obtained value was less than 1%, it was judged to be below the measurement limit, and was described as "less than 1%". The average value of N=3 was taken as the water content. The water content of the substrate having the hydrophilic polymer layer, that is, the medical device was calculated in the same manner.
Water content (%) of base material=100×(Ww−Wd)/Ww Formula (1).

<Change in water content of base material before and after formation of hydrophilic polymer layer>
From the measurement results of the water content of the base material and the medical device, the change amount of the water content was calculated by the following formula (2). Amount of change in water content of the base material before and after formation of the hydrophilic polymer layer (percentage point)=water content of medical device (mass %)-water content of base material (mass %) Formula (2).

<Contact angle>
As a sample, a strip-shaped test piece having a size of about 5 mm×10 mm×0.1 mm cut out from a contact lens-shaped sample was used, and a dynamic contact angle when advancing to a phosphate buffer was measured by a wettability tester WET-6200. (Manufactured by Resca Co., Ltd.). The immersion speed was 0.1 mm/sec and the immersion depth was 7 mm.

<Friction coefficient>
Under the following conditions, the friction coefficient of the surface of the medical device wet with the phosphate buffer solution (preservation solution in the package in the case of measuring a commercial contact lens) was measured at N=5, and the average value was taken as the friction coefficient.
Device: Friction tester KES-SE (manufactured by Kato Tech Co., Ltd.)
Friction SENS: H
Measurement SPEED: 2×1 mm/sec
Friction load: 44 g.

<Amount of lipid attached>
A 20 cc screw tube was charged with 0.03 g of methyl palmitate, 10 g of pure water, and one contact lens-shaped sample. The screw tube was shaken for 3 hours at 37° C. and 165 rpm. After shaking, the sample in the screw tube was scrubbed with tap water at 40° C. and a household liquid detergent (“Mama Lemon (registered trademark)” manufactured by Lion). The washed sample was placed in a screw tube containing a phosphate buffer and stored in a refrigerator at 4°C for 1 hour. Then, the sample was visually observed, and if there was a cloudy portion, it was determined that methyl palmitate was attached, and the area of the portion where methyl palmitate was attached to the entire surface of the sample was observed.

<Amount of mucin attached>
A test piece having a width (minimum portion) of 5 mm and a length of 14 mm was cut out from a contact lens-shaped sample using a specified punching die. As the mucin, Mucin, Bovine Submaxillary Ground (Catalog No. 499643) from CALBIOCHEM was used. The test piece was immersed in a 0.1% concentration mucin aqueous solution for 20 hours at 37° C., and then the amount of mucin attached to the sample was quantified by the BCA (bicinchoninic acid) protein assay method. The average value of N=3 was taken as the mucin adhesion amount.

<Tensile modulus>
A test piece having a width (minimum portion) of 5 mm and a length of 14 mm was cut out from a contact lens-shaped substrate using a specified punching die. Using the test piece, a tensile test was carried out using Tensilon RTG-1210 manufactured by A&D Co., Ltd. The pulling speed was 100 mm/min, and the distance between grips (initial) was 5 mm. The measurements were performed on both the substrate before formation of the hydrophilic polymer layer and the medical device after formation of the hydrophilic polymer layer. The measurement was performed at N=8, and the average value of the values of N=6 excluding the maximum value and the minimum value was taken as the tensile elastic modulus. The tensile modulus was also measured for the substrate having the hydrophilic polymer layer, that is, the medical device.

<Ratio of change in tensile elastic modulus of base material before and after formation of hydrophilic polymer layer>
From the measurement results of the tensile elastic modulus of the above-mentioned base material and medical device, it was calculated by the following formula (3). The average value of N=6 was taken as the rate of change in tensile modulus before and after the formation of the hydrophilic polymer layer.
Rate of change in tensile elastic modulus of base material before and after formation of hydrophilic polymer layer (%)=(tensile elastic modulus of medical device after formation of hydrophilic polymer layer−tensile elastic modulus of base material before formation of hydrophilic polymer layer)/hydrophilicity Elastic modulus of the base material before forming the water-soluble polymer layer×100 Formula (3).

<size>
The diameter of a contact lens-shaped substrate (N=3) was measured, and the average value was used as the size. The size of the substrate having the hydrophilic polymer layer, that is, the medical device was measured in the same manner.

<Size change rate before and after formation of hydrophilic polymer layer>
It was calculated by the following formula (4) from the measurement results of the sizes of the base material and the medical device. The average value of N=3 was taken as the size change rate before and after the formation of the hydrophilic polymer layer.

Size change rate (%) before and after formation of hydrophilic polymer layer=(size of device after formation of hydrophilic polymer layer−size of substrate before formation of hydrophilic polymer layer)/before formation of hydrophilic polymer layer Substrate size x 100 Formula (4).

<Molecular weight measurement>
The molecular weight of the hydrophilic polymer was measured under the following conditions.
Device: Shimadzu Prominence GPC system Pump: LC-20AD
Autosampler: SIL-20AHT
Column oven: CTO-20A
Detector: RID-10A
Column: Tosoh GMPWXL (inner diameter 7.8 mm×30 cm, particle diameter 13 μm)
Solvent: Water/methanol=1/1 (0.1N lithium nitrate added)
Flow rate: 0.5 mL/min Measurement time: 30 minutes Sample concentration: 0.1-0.3 mass%
Sample injection volume: 100 μL
Standard sample: polyethylene oxide standard sample (0.1 kD to 1258 kD) manufactured by Agilent.

<pH measuring method>
The pH of the solution was measured using a pH meter Eutech pH2700 (manufactured by Eutech Instruments). In the table, as for the initial pH of the solution containing the hydrophilic polymer, after adding all of the hydrophilic polymer to the solution described in each Example, the solution was stirred at room temperature (23 to 25° C.) for 2 hours with a rotor to prepare the solution. It was made uniform and then measured. Further, in the table, “pH after heat treatment” is the pH measured immediately after cooling the solution to room temperature (23 to 25° C.) after performing heat treatment once.

<Judgment of separation of hydrophilic polymer layer>
Whether or not the hydrophilic polymer layer was separated into two or more layers was determined by observing the cross section of the medical device using a transmission electron microscope.
Equipment: Transmission electron microscope Conditions: Accelerating voltage 100kV
Sample preparation: Sample preparation was performed by the ultrathin section method using RuO ₄ staining. When it is difficult to distinguish between the substrate and the hydrophilic polymer layer, OsO ₄ dyeing may be added. In this example, RuO ₄ dyeing was performed when the substrate was a silicone hydrogel type or a silicone type.
An ultramicrotome was used for the production of ultrathin sections.

<Analysis of elemental composition of hydrophilic polymer layer>
The elemental composition analysis of the hydrophilic polymer layer was performed by analyzing a cross section of the medical device frozen in a water-containing state using a cryotransfer holder by a scanning transmission electron microscope and electron energy loss spectroscopy.
Device: Field emission electron microscope Accelerating voltage: 200 kV
Measurement temperature: -100℃
Electron Energy Loss Spectroscopy: GATAN GIF Tridiem
Image acquisition: Digital Micrograph
Sample preparation: Sample preparation was performed by the ultrathin section method using RuO ₄ staining. When it is difficult to distinguish between the base material and the coat layer, OsO ₄ dyeing may be added. In this example, RuO ₄ dyeing was performed when the substrate was a silicone hydrogel type or a silicone type.
An ultramicrotome was used for the production of ultrathin sections.

<Film thickness of hydrophilic polymer layer>
The film thickness of the dry hydrophilic polymer layer was determined by observing a cross section of the dry medical device using a transmission electron microscope. The measurement was performed under the conditions described in <Judgment of separation of hydrophilic polymer layer> above. The film thickness was measured at 5 locations for each visual field while changing the locations at 4 locations, and the average value of the thicknesses at 20 locations was recorded.

The thickness of the hydrophilic polymer layer in the frozen state was determined by observing the cross section of the medical device frozen in the water containing state using a cryotransfer holder using a scanning transmission electron microscope. The measurement was performed under the conditions described in <Analysis of elemental composition of hydrophilic polymer layer>. The film thickness was measured at 5 places for each visual field by changing 4 places, and the film thickness was measured at 20 places in total. The minimum and maximum values of the measured film thickness are listed.

<Difference in average thickness of hydrophilic polymer layer>
The average thickness of the hydrophilic polymer layer was measured under the conditions described in the film thickness measurement of the hydrophilic polymer layer in the dry state in <Film thickness of hydrophilic polymer layer> above. The difference in the average thickness was calculated by the following formula (5) as a ratio of the average thickness of the front curve surface and the average thickness of the base curve surface to the thinner one.
Difference in average thickness (%)=(average film thickness of surface having large average thickness−average film thickness of surface having thin average thickness)/average film thickness of surface having thin average thickness×100 Formula (5).

[Reference Example 1]
28 parts by mass of polydimethylsiloxane having a methacryloyl group at both ends represented by formula (M1) (FM7726, JNC Corporation, Mw: 30,000), silicone monomer represented by formula (M2) (FM0721, JNC stock) Company, Mw: 5,000) 7 parts by mass, trifluoroethyl acrylate (Viscoat (registered trademark) 3F, Osaka Organic Chemical Industry Co., Ltd.) 57.9 parts by mass, 2-ethylhexyl acrylate (Tokyo Kasei Kogyo Co., Ltd.) 7 parts by mass and 0.1 part by mass of dimethylaminoethyl acrylate (Kojin Co., Ltd.), and 5,000 ppm of photoinitiator Irgacure (registered trademark) 819 (Nagase Sangyo Co., Ltd.) and ultraviolet light based on the total mass of these monomers An absorber (RUVA-93, Otsuka Chemical) 5,000 ppm, a colorant (RB246, Arran chemical) 100 ppm were prepared, and further 10 parts by mass of t-amyl alcohol was prepared with respect to 100 parts by mass of the total amount of the monomers. All of these were mixed and stirred. The agitated mixture was filtered with a membrane filter (pore size: 0.45 μm) to remove the insoluble matter to obtain a monomer mixture.

The above monomer mixture was injected into a contact lens mold made of transparent resin (material on the base curve side: polypropylene, material on the front curve side: polypropylene), and light irradiation (wavelength 405 nm (±5 nm), illuminance: 0 to 0.7 mW) /Cm ² , 30 minutes) and polymerized to obtain a molded body made of a low hydrous soft material containing silicon atoms.

After the polymerization, the obtained molded body, together with the mold with the front curve and the base curve released, was immersed in a 100% by mass isopropyl alcohol aqueous solution at 60° C. for 1.5 hours to form a contact lens-shaped molded body from the mold. Peeled off. The obtained molded body was immersed in a large excess amount of 100 mass% isopropyl alcohol aqueous solution kept at 60° C. for 2 hours to extract impurities such as residual monomers. Then, it was dried at room temperature (23° C.) for 12 hours.

[Phosphate buffer]
The compositions of the phosphate buffers used in the processes of the following Examples and Comparative Examples and the above-described measurement are as follows.
KCl 0.2g/L
KH ₂ PO ₄ 0.2 g/L
NaCl 8.0 g/L
Na ₂ HPO ₄ (anhydrous) 1.15 g/L
EDTA 0.25 g/L.

[Example 1]
The molded body obtained in Reference Example 1 was used as the base material. Acrylic acid/N,N-dimethylacrylamide copolymer (number ratio of basic group/acidic group 0, molar ratio in copolymerization 1/9, Mw:800,000, manufactured by Osaka Organic Chemical Industry Co., Ltd.) was purified water. The pH of the aqueous solution containing 0.2 mass% was adjusted to 2.6 with sulfuric acid. The substrate was immersed in the solution and heated in an autoclave at 121°C for 30 minutes. The obtained molded body was immersed and washed in a phosphate buffer for 30 seconds, replaced with a new phosphate buffer, and further heated at 121° C. for 30 minutes in an autoclave. Tables 1 to 4 show the results of evaluation of the obtained molded body by the above method.

[Example 2]
The molded body obtained in Reference Example 1 was used as the base material. Acrylic acid/N,N-dimethylacrylamide copolymer (number ratio of basic group/acidic group 0, molar ratio in copolymerization 1/9, Mw: 700,000, manufactured by Osaka Organic Chemical Industry Co., Ltd.) was used as phosphoric acid. The solution containing 0.2% by mass in the buffer was adjusted to pH 2.7 with sulfuric acid. The substrate was immersed in the solution and heated in an autoclave at 121°C for 30 minutes. The obtained molded body was washed with a phosphate buffer solution by shaking at 250 rpm for 10 seconds, replaced with a new phosphate buffer solution, and further heated at 121° C. for 30 minutes in an autoclave. Tables 1 to 4 show the results of evaluation of the obtained molded body by the above method.

[Example 3]
The molded body obtained in Reference Example 1 was used as the base material. Acrylic acid/N,N-dimethylacrylamide copolymer (number ratio of basic group/acidic group 0, molar ratio in copolymerization 1/2, Mw:500,000, manufactured by Osaka Organic Chemical Industry Co., Ltd.) was used as phosphoric acid. The solution containing 0.03% by mass in the buffer was adjusted to pH 3.1 with sulfuric acid. The substrate was immersed in the solution and heated in an autoclave at 121°C for 30 minutes. The obtained molded body was washed with a phosphate buffer solution by shaking at 250 rpm for 10 seconds, replaced with a new phosphate buffer solution, and further heated at 121° C. for 30 minutes in an autoclave. Tables 1 to 4 show the results of evaluation of the obtained molded body by the above method.

[Example 4]
The molded body obtained in Reference Example 1 was used as the base material. Acrylic acid/N,N-dimethylacrylamide copolymer (number ratio of basic group/acidic group 0, molar ratio in copolymerization 1/9, Mw:800,000, manufactured by Osaka Organic Chemical Industry Co., Ltd.) was used as phosphoric acid. The solution containing 0.2% by mass in the buffer was adjusted to pH 2.4 with sulfuric acid. The substrate was immersed in the solution and heated at 80° C. for 30 minutes in an autoclave. The obtained molded body was washed with a phosphate buffer solution by shaking at 250 rpm for 10 seconds, replaced with a new phosphate buffer solution, and further heated at 121° C. for 30 minutes in an autoclave. Tables 1 to 4 show the evaluation results of the obtained molded product by the above method.

[Example 5]
The molded body obtained in Reference Example 1 was used as the base material. Acrylic acid/N,N-dimethylacrylamide copolymer (number ratio of basic group/acidic group 0, molar ratio in copolymerization 1/9, Mw:800,000, manufactured by Osaka Organic Chemical Industry Co., Ltd.) was used as phosphoric acid. The solution containing 0.2% by mass in the buffer was adjusted to pH 2.4 with sulfuric acid. The substrate was immersed in the solution and heated at 100° C. for 30 minutes in an autoclave. The obtained molded body was washed with a phosphate buffer solution by shaking at 250 rpm for 10 seconds, replaced with a new phosphate buffer solution, and further heated at 121° C. for 30 minutes in an autoclave. Tables 1 to 4 show the results of evaluation of the obtained molded body by the above method.

[Example 6]
The molded body obtained in Reference Example 1 was used as the base material. Acrylic acid/N,N-dimethylacrylamide copolymer (number ratio of basic group/acidic group 0, molar ratio in copolymerization 1/9, Mw:800,000, manufactured by Osaka Organic Chemical Industry Co., Ltd.) was purified water. The pH of the aqueous solution containing 0.2 mass% was adjusted to 2.4 with sulfuric acid. The substrate was immersed in the solution and heated in an autoclave at 121°C for 30 minutes. The obtained molded body was washed with a phosphate buffer solution by shaking at 250 rpm for 10 seconds, replaced with a new phosphate buffer solution, and further heated at 121° C. for 30 minutes in an autoclave. Tables 1 to 4 show the results of evaluation of the obtained molded body by the above method.

[Example 7]
As a base material, a commercially available hydrogel lens "1day Acuvue (registered trademark)" containing 2-hydroxyethyl methacrylate as a main component (manufactured by Johnson & Johnson, etafilcon A) was used. Acrylic acid/vinylpyrrolidone copolymer (basic group/acidic group number ratio 0, molar ratio in copolymerization 1/4, Mw:500,000, manufactured by Osaka Organic Chemical Industry Co., Ltd.) in a phosphate buffer solution The solution containing 0.1% by mass was adjusted to pH 3.1 with sulfuric acid. The substrate was immersed in the solution and heated in an autoclave at 121°C for 30 minutes. The obtained molded body was washed with a phosphate buffer solution by shaking at 250 rpm for 10 seconds, replaced with a new phosphate buffer solution, and further heated at 121° C. for 30 minutes in an autoclave. Tables 1 to 4 show the results of evaluation of the obtained molded body by the above method.

[Example 8]
As a base material, a commercially available hydrogel lens "1day Acuvue (registered trademark)" containing 2-hydroxyethyl methacrylate as a main component (manufactured by Johnson & Johnson, etafilcon A) was used. Acrylic acid/vinylpyrrolidone copolymer (basic group/acidic group number ratio 0, molar ratio in copolymerization 1/4, Mw:500,000, manufactured by Osaka Organic Chemical Industry Co., Ltd.) in a phosphate buffer solution The solution containing 0.1% by mass was adjusted to pH 4.1 with sulfuric acid. The substrate was immersed in the solution and heated in an autoclave at 121°C for 30 minutes. The obtained molded body was washed with a phosphate buffer solution by shaking at 250 rpm for 10 seconds, replaced with a new phosphate buffer solution, and further heated at 121° C. for 30 minutes in an autoclave. Tables 1 to 4 show the evaluation results of the obtained molded product by the above method.

[Example 9]
As a base material, a commercially available hydrogel lens "1day Acuvue (registered trademark)" containing 2-hydroxyethyl methacrylate as a main component (manufactured by Johnson & Johnson, etafilcon A) was used. Acrylic acid/vinylpyrrolidone copolymer (basic group/acidic group number ratio 0, molar ratio in copolymerization 1/4, Mw:500,000, manufactured by Osaka Organic Chemical Industry Co., Ltd.) in a phosphate buffer solution The solution containing 0.1 mass% was adjusted to pH 5.0 with sulfuric acid. The substrate was immersed in the solution and heated in an autoclave at 121°C for 30 minutes. The obtained molded body was washed with a phosphate buffer solution by shaking at 250 rpm for 10 seconds, replaced with a new phosphate buffer solution, and further heated at 121° C. for 30 minutes in an autoclave. Tables 1 to 4 show the results of evaluation of the obtained molded body by the above method.

[Example 10]
As a base material, a commercially available hydrogel lens "1day Acuvue (registered trademark)" containing 2-hydroxyethyl methacrylate as a main component (manufactured by Johnson & Johnson, etafilcon A) was used. Acrylic acid/vinylpyrrolidone copolymer (basic group/acidic group number ratio 0, molar ratio in copolymerization 1/4, Mw:500,000, manufactured by Osaka Organic Chemical Industry Co., Ltd.) in a phosphate buffer solution The solution containing 0.1% by mass was adjusted to pH 5.7 with sulfuric acid. The substrate was immersed in the solution and heated in an autoclave at 121°C for 30 minutes. The obtained molded body was washed with a phosphate buffer solution by shaking at 250 rpm for 10 seconds, replaced with a new phosphate buffer solution, and further heated at 121° C. for 30 minutes in an autoclave. Tables 1 to 4 show the results of evaluation of the obtained molded body by the above method.

[Example 11]
As a base material, a commercially available hydrogel lens "1day Acuvue (registered trademark)" containing 2-hydroxyethyl methacrylate as a main component (manufactured by Johnson & Johnson, etafilcon A) was used. Acrylic acid/N,N-dimethylacrylamide copolymer (number ratio of basic group/acidic group 0, molar ratio in copolymerization 1/9, Mw:800,000, manufactured by Osaka Organic Chemical Industry Co., Ltd.) was used as phosphoric acid. The solution containing 0.2% by mass in the buffer was adjusted to pH 3.3 with sulfuric acid. The substrate was immersed in the solution and heated in an autoclave at 121°C for 30 minutes. The obtained molded body was washed with a phosphate buffer solution by shaking at 250 rpm for 10 seconds, replaced with a new phosphate buffer solution, and further heated at 121° C. for 30 minutes in an autoclave. Tables 1 to 4 show the results of evaluation of the obtained molded body by the above method.

[Example 12]
As a base material, a commercially available hydrogel lens "1day Acuvue (registered trademark)" containing 2-hydroxyethyl methacrylate as a main component (manufactured by Johnson & Johnson, etafilcon A) was used. Acrylic acid/N,N-dimethylacrylamide copolymer (number ratio of basic group/acidic group 0, molar ratio in copolymerization 1/9, Mw:500,000, manufactured by Osaka Organic Chemical Industry Co., Ltd.) was used as phosphoric acid. The solution containing 0.2% by mass in the buffer was adjusted to pH 3.0 with sulfuric acid. The substrate was immersed in the solution and heated in an autoclave at 121°C for 30 minutes. The obtained molded body was washed with a phosphate buffer solution by shaking at 250 rpm for 10 seconds, replaced with a new phosphate buffer solution, and further heated at 121° C. for 30 minutes in an autoclave. Tables 1 to 4 show the results of evaluation of the obtained molded body by the above method.

[Example 13]
As a base material, a commercially available hydrogel lens "1day Acuvue (registered trademark)" containing 2-hydroxyethyl methacrylate as a main component (manufactured by Johnson & Johnson, etafilcon A) was used. Acrylic acid/N,N-dimethylacrylamide copolymer (number ratio of basic group/acidic group 0, molar ratio in copolymerization 1/2, Mw: 700,000, manufactured by Osaka Organic Chemical Industry Co., Ltd.) was used as phosphoric acid. The solution containing 0.2% by mass in the buffer was adjusted to pH 3.0 with sulfuric acid. The substrate was immersed in the solution and heated in an autoclave at 121°C for 30 minutes. The obtained molded body was washed with a phosphate buffer solution by shaking at 250 rpm for 10 seconds, replaced with a new phosphate buffer solution, and further heated at 121° C. for 30 minutes in an autoclave. Tables 1 to 4 show the results of evaluation of the obtained molded body by the above method.

[Example 14]
As a base material, a commercially available hydrogel lens "1day Acuvue (registered trademark)" containing 2-hydroxyethyl methacrylate as a main component (manufactured by Johnson & Johnson, etafilcon A) was used. Acrylic acid/vinylpyrrolidone copolymer (basic group/acidic group number ratio 0, molar ratio in copolymerization 1/4, Mw:500,000, manufactured by Osaka Organic Chemical Industry Co., Ltd.) in a phosphate buffer solution The solution containing 0.1 mass% was adjusted to pH 4.0 with sulfuric acid. The substrate was immersed in the solution and heated in an autoclave at 121°C for 30 minutes. The obtained molded body was washed with a phosphate buffer solution by shaking at 250 rpm for 10 seconds, replaced with a new phosphate buffer solution, and further heated at 121° C. for 30 minutes in an autoclave. Tables 1 to 4 show the results of evaluation of the obtained molded body by the above method.

[Example 15]
As a base material, a commercially available hydrogel lens "1day Acuvue (registered trademark)" containing 2-hydroxyethyl methacrylate as a main component (manufactured by Johnson & Johnson, etafilcon A) was used. Acrylic acid/vinylpyrrolidone copolymer (basic group/acidic group number ratio 0, molar ratio in copolymerization 1/4, Mw: 800,000, manufactured by Osaka Organic Chemical Industry Co., Ltd.) in a phosphate buffer solution The solution containing 0.1 mass% was adjusted to pH 4.0 with sulfuric acid. The substrate was immersed in the solution and heated in an autoclave at 121°C for 30 minutes. The obtained molded body was washed with a phosphate buffer solution by shaking at 250 rpm for 10 seconds, replaced with a new phosphate buffer solution, and further heated at 121° C. for 30 minutes in an autoclave. Tables 1 to 4 show the results of evaluation of the obtained molded body by the above method.

[Example 16]
As a base material, a commercially available hydrogel lens "1day Acuvue (registered trademark)" containing 2-hydroxyethyl methacrylate as a main component (manufactured by Johnson & Johnson, etafilcon A) was used. Acrylic acid/vinylpyrrolidone copolymer (basic group/acidic group number ratio 0, molar ratio in copolymerization 1/9, Mw:500,000, manufactured by Osaka Organic Chemical Industry Co., Ltd.) in a phosphate buffer solution The solution containing 0.1% by mass was immersed in a solution adjusted to pH 4.0 with sulfuric acid and heated at 121° C. for 30 minutes in an autoclave. The obtained molded body was washed with a phosphate buffer solution by shaking at 250 rpm for 10 seconds, replaced with a new phosphate buffer solution, and further heated at 121° C. for 30 minutes in an autoclave. Tables 1 to 4 show the results of evaluation of the obtained molded body by the above method.

[Example 17]
A commercially available silicone hydrogel lens "1day Acuvue TruEye (registered trademark)" (manufactured by Johnson & Johnson, narafilcon A) containing polyvinylpyrrolidone and silicone as main components was used as a base material. Acrylic acid/N,N-dimethylacrylamide copolymer (number ratio of basic group/acidic group 0, molar ratio in copolymerization 1/9, Mw:800,000, manufactured by Osaka Organic Chemical Industry Co., Ltd.) was used as phosphoric acid. The solution containing 0.2% by mass in the buffer was adjusted to pH 3.0 with sulfuric acid. The substrate was immersed in the solution and heated in an autoclave at 121°C for 30 minutes. The obtained molded body was washed with a phosphate buffer solution by shaking at 250 rpm for 10 seconds, replaced with a new phosphate buffer solution, and further heated at 121° C. for 30 minutes in an autoclave. Tables 1 to 4 show the results of evaluation of the obtained molded body by the above method.

[Example 18]
A commercially available silicone hydrogel lens "1day Acuvue TruEye (registered trademark)" (manufactured by Johnson & Johnson, narafilcon A) containing polyvinylpyrrolidone and silicone as main components was used as a base material. Acrylic acid/N,N-dimethylacrylamide copolymer (number ratio of basic group/acidic group 0, molar ratio in copolymerization 1/9, Mw:500,000, manufactured by Osaka Organic Chemical Industry Co., Ltd.) was used as phosphoric acid. The solution containing 0.2% by mass in the buffer was adjusted to pH 3.0 with sulfuric acid. The substrate was immersed in the solution and heated in an autoclave at 121°C for 30 minutes. The obtained molded body was washed with a phosphate buffer solution by shaking at 250 rpm for 10 seconds, replaced with a new phosphate buffer solution, and further heated at 121° C. for 30 minutes in an autoclave. Tables 1 to 4 show the results of evaluation of the obtained molded body by the above method.

[Example 19]
As a base material, a commercially available silicone hydrogel lens "MyDay (registered trademark)" (manufactured by Cooper Vision, stenfilcon A) containing silicone as a main component was used. Acrylic acid/N,N-dimethylacrylamide copolymer (number ratio of basic group/acidic group 0, molar ratio in copolymerization 1/9, Mw:800,000, manufactured by Osaka Organic Chemical Industry Co., Ltd.) was used as phosphoric acid. The solution containing 0.2% by mass in the buffer was adjusted to pH 2.0 with citric acid. The substrate was immersed in the solution and heated in an autoclave at 90°C for 30 minutes. The obtained molded body was washed with a phosphate buffer solution by shaking at 250 rpm for 10 seconds, replaced with a new phosphate buffer solution, and further heated at 121° C. for 30 minutes in an autoclave. Tables 1 to 4 show the results of evaluation of the obtained molded body by the above method.

[Example 20]
As a base material, a commercially available silicone hydrogel lens "MyDay (registered trademark)" (manufactured by Cooper Vision, stenfilcon A) containing silicone as a main component was used. Acrylic acid/N,N-dimethylacrylamide copolymer (number ratio of basic group/acidic group 0, molar ratio in copolymerization 1/9, Mw:800,000, manufactured by Osaka Organic Chemical Industry Co., Ltd.) was used as phosphoric acid. The solution containing 0.2% by mass of the buffer solution was adjusted to pH 2.2 with citric acid. The substrate was immersed in the solution and heated in an autoclave at 90°C for 30 minutes. The obtained molded body was washed with a phosphate buffer solution by shaking at 250 rpm for 10 seconds, replaced with a new phosphate buffer solution, and further heated at 121° C. for 30 minutes in an autoclave. Tables 1 to 4 show the results of evaluation of the obtained molded body by the above method.

[Example 21]
As a base material, a commercially available silicone hydrogel lens "MyDay (registered trademark)" (manufactured by Cooper Vision, stenfilcon A) containing silicone as a main component was used. Acrylic acid/N,N-dimethylacrylamide copolymer (number ratio of basic group/acidic group 0, molar ratio in copolymerization 1/9, Mw:800,000, manufactured by Osaka Organic Chemical Industry Co., Ltd.) was used as phosphoric acid. The solution containing 0.4% by mass of the buffer solution was adjusted to pH 2.0 with citric acid. The substrate was immersed in the solution and heated in an autoclave at 90°C for 30 minutes. The obtained molded body was washed with a phosphate buffer solution by shaking at 250 rpm for 10 seconds, replaced with a new phosphate buffer solution, and further heated at 121° C. for 30 minutes in an autoclave. Tables 1 to 4 show the results of evaluation of the obtained molded body by the above method.

[Example 22]
A commercially available silicone hydrogel lens "1day Acuvue TruEye (registered trademark)" (manufactured by Johnson & Johnson, narafilcon A) containing polyvinylpyrrolidone and silicone as main components was used as a base material. Acrylic acid/vinylpyrrolidone/N,N-dimethylacrylamide copolymer (number ratio of basic group/acidic group 0, molar ratio in copolymerization 1/1/8, Mw:500,000, Osaka Organic Chemical Industry Co., Ltd. (Manufactured by Mitsui Chemicals Co., Ltd.) in an amount of 0.2% by mass in a phosphate buffer was adjusted to pH 2.6 with sulfuric acid. The substrate was immersed in the solution and heated in an autoclave at 121°C for 30 minutes. The obtained molded body was immersed and washed in a phosphate buffer for 30 seconds, replaced with a new phosphate buffer, and further heated at 121° C. for 30 minutes in an autoclave. Tables 5 to 8 show the results of evaluation of the obtained molded product by the above method.

[Example 23]
As a base material, a commercially available silicone hydrogel lens "MyDay (registered trademark)" (manufactured by Cooper Vision, stenfilcon A) containing silicone as a main component was used. Acrylic acid/2-hydroxyethyl methacrylate/N,N-dimethylacrylamide copolymer (number ratio of basic group/acidic group 0, molar ratio in copolymerization 1/1/8, Mw:500,000, Osaka Organic Chemical Industry Co., Ltd.) was added to a phosphate buffer solution in an amount of 0.2% by mass to adjust the pH to 2.6 with sulfuric acid. The substrate was immersed in the solution and heated in an autoclave at 121°C for 30 minutes. The obtained molded body was immersed and washed in a phosphate buffer for 30 seconds, replaced with a new phosphate buffer, and further heated at 121° C. for 30 minutes in an autoclave. Tables 5 to 8 show the results of evaluation of the obtained molded product by the above method.

[Example 24]
As a base material, a commercially available silicone hydrogel lens "MyDay (registered trademark)" (manufactured by Cooper Vision, stenfilcon A) containing silicone as a main component was used. Acrylic acid/2-hydroxyethyl methacrylate/N,N-dimethylacrylamide copolymer (number ratio of basic group/acidic group 0, molar ratio in copolymerization 1/1/8, Mw:500,000, Osaka Organic Chemical solution) (0.2 mass% in phosphate buffer) was adjusted to pH 3.1 with citric acid. The substrate was immersed in the solution and heated in an autoclave at 121°C for 30 minutes. The obtained molded body was immersed and washed in a phosphate buffer for 30 seconds, replaced with a new phosphate buffer, and further heated at 121° C. for 30 minutes in an autoclave. Tables 5 to 8 show the results of evaluation of the obtained molded product by the above method.

[Example 25]
As a base material, a commercially available silicone hydrogel lens "MyDay (registered trademark)" (manufactured by Cooper Vision, stenfilcon A) containing silicone as a main component was used. Acrylic acid/N,N-dimethylacrylamide copolymer (number ratio of basic group/acidic group 0, molar ratio in copolymerization 1/9, Mw:800,000, manufactured by Osaka Organic Chemical Industry Co., Ltd.) was used as phosphoric acid. An aqueous solution containing 0.2% by mass of the buffer solution was adjusted to pH 3.1 with citric acid. The substrate was immersed in the solution and heated in an autoclave at 121°C for 30 minutes. The obtained molded body was immersed and washed in a phosphate buffer for 30 seconds, replaced with a new phosphate buffer, and further heated at 121° C. for 30 minutes in an autoclave. Tables 5 to 8 show the results of evaluation of the obtained molded product by the above method.

[Example 26]
A commercially available silicone hydrogel lens "Biofinity (registered trademark)" (comfilcon A, manufactured by Cooper Vision Corp.) containing silicone as a main component was used as a base material. Acrylic acid/2-hydroxyethyl methacrylate/N,N-dimethylacrylamide copolymer (number ratio of basic group/acidic group 0, molar ratio in copolymerization 1/1/8, Mw:500,000, Osaka Organic Chemical Industry Co., Ltd.) was added to a phosphoric acid buffer solution in an amount of 0.2% by mass to adjust the pH to 2.9 with sulfuric acid. The substrate was immersed in the solution and heated in an autoclave at 121°C for 30 minutes. The obtained molded body was immersed and washed in a phosphate buffer for 30 seconds, replaced with a new phosphate buffer, and further heated at 121° C. for 30 minutes in an autoclave. Tables 5 to 8 show the results of evaluation of the obtained molded product by the above method.

[Example 27]
A commercially available silicone hydrogel lens "Biofinity (registered trademark)" (comfilcon A, manufactured by Cooper Vision Corp.) containing silicone as a main component was used as a base material. Acrylic acid/2-hydroxyethyl methacrylate/N,N-dimethylacrylamide copolymer (number ratio of basic group/acidic group 0, molar ratio in copolymerization 1/1/8, Mw:500,000, Osaka Organic Chemical solution) (0.2 mass% in phosphate buffer) was adjusted to pH 3.3 with citric acid. The substrate was immersed in the solution and heated in an autoclave at 121°C for 30 minutes. The obtained molded body was immersed and washed in a phosphate buffer for 30 seconds, replaced with a new phosphate buffer, and further heated at 121° C. for 30 minutes in an autoclave. Tables 5 to 8 show the results of evaluation of the obtained molded product by the above method.

[Example 28]
A commercially available silicone hydrogel lens "Biofinity (registered trademark)" (comfilcon A, manufactured by Cooper Vision Corp.) containing silicone as a main component was used as a base material. Acrylic acid/vinylpyrrolidone/N,N-dimethylacrylamide copolymer (number ratio of basic group/acidic group 0, molar ratio in copolymerization 1/1/8, Mw:500,000, Osaka Organic Chemical Industry Co., Ltd. (Manufactured by Mitsui Chemicals, Inc.) in an amount of 0.2% by mass in a phosphate buffer was adjusted to pH 3.1 with citric acid. The substrate was immersed in the solution and heated in an autoclave at 121°C for 30 minutes. The obtained molded body was immersed and washed in a phosphate buffer for 30 seconds, replaced with a new phosphate buffer, and further heated at 121° C. for 30 minutes in an autoclave. Tables 5 to 8 show the results of evaluation of the obtained molded product by the above method.

Example 29
A commercially available silicone hydrogel lens "Biofinity (registered trademark)" (comfilcon A, manufactured by Cooper Vision Corp.) containing silicone as a main component was used as a base material. Acrylic acid/N,N-dimethylacrylamide copolymer (number ratio of basic group/acidic group 0, molar ratio in copolymerization 1/9, Mw:800,000, manufactured by Osaka Organic Chemical Industry Co., Ltd.) was used as phosphoric acid. An aqueous solution containing 0.2% by mass of the buffer solution was adjusted to pH 3.2 with citric acid. The substrate was immersed in the solution and heated in an autoclave at 121°C for 30 minutes. The obtained molded body was immersed and washed in a phosphate buffer for 30 seconds, replaced with a new phosphate buffer, and further heated at 121° C. for 30 minutes in an autoclave. Tables 5 to 8 show the results of evaluation of the obtained molded product by the above method.

[Example 30]
As a base material, a commercially available silicone hydrogel lens "MyDay (registered trademark)" (manufactured by Cooper Vision, stenfilcon A) containing silicone as a main component was used. Acrylic acid/N,N-dimethylacrylamide copolymer (number ratio of basic group/acidic group 0, molar ratio in copolymerization 1/9, Mw:800,000, manufactured by Osaka Organic Chemical Industry Co., Ltd.) was used as phosphoric acid. An aqueous solution containing 0.2% by mass of the buffer solution was adjusted to pH 3.2 with formic acid. The substrate was immersed in the solution and heated in an autoclave at 121°C for 30 minutes. The obtained molded body was immersed and washed in a phosphate buffer for 30 seconds, replaced with a new phosphate buffer, and further heated at 121° C. for 30 minutes in an autoclave. Tables 5 to 8 show the results of evaluation of the obtained molded product by the above method.

[Example 31]
As a base material, a commercially available silicone hydrogel lens "MyDay (registered trademark)" (manufactured by Cooper Vision, stenfilcon A) containing silicone as a main component was used. Acrylic acid/N,N-dimethylacrylamide copolymer (number ratio of basic group/acidic group 0, molar ratio in copolymerization 1/9, Mw:800,000, manufactured by Osaka Organic Chemical Industry Co., Ltd.) was used as phosphoric acid. An aqueous solution containing 0.2% by mass of the buffer solution was adjusted to pH 3.2 with acetic acid. The substrate was immersed in the solution and heated in an autoclave at 121°C for 30 minutes. The obtained molded body was immersed and washed in a phosphate buffer for 30 seconds, replaced with a new phosphate buffer, and further heated at 121° C. for 30 minutes in an autoclave. Tables 5 to 8 show the results of evaluation of the obtained molded product by the above method.

[Example 32]
As a base material, a commercially available silicone hydrogel lens "MyDay (registered trademark)" (manufactured by Cooper Vision, stenfilcon A) containing silicone as a main component was used. Acrylic acid/N,N-dimethylacrylamide copolymer (number ratio of basic group/acidic group 0, molar ratio in copolymerization 1/9, Mw:800,000, manufactured by Osaka Organic Chemical Industry Co., Ltd.) was used as phosphoric acid. An aqueous solution containing 0.2% by mass of the buffer solution was adjusted to pH 3.2 with propionic acid. The substrate was immersed in the solution and heated in an autoclave at 121°C for 30 minutes. The obtained molded body was immersed and washed in a phosphate buffer for 30 seconds, replaced with a new phosphate buffer, and further heated at 121° C. for 30 minutes in an autoclave. Tables 5 to 8 show the results of evaluation of the obtained molded product by the above method.

[Example 33]
As a base material, a commercially available silicone hydrogel lens "MyDay (registered trademark)" (manufactured by Cooper Vision, stenfilcon A) containing silicone as a main component was used. Acrylic acid/N,N-dimethylacrylamide copolymer (number ratio of basic group/acidic group 0, molar ratio in copolymerization 1/9, Mw:800,000, manufactured by Osaka Organic Chemical Industry Co., Ltd.) was used as phosphoric acid. An aqueous solution containing 0.2% by mass of the buffer solution was adjusted to pH 3.2 with butyric acid. The substrate was immersed in the solution and heated in an autoclave at 121°C for 30 minutes. The obtained molded body was immersed and washed in a phosphate buffer for 30 seconds, replaced with a new phosphate buffer, and further heated at 121° C. for 30 minutes in an autoclave. Tables 5 to 8 show the results of evaluation of the obtained molded product by the above method.

Example 34
As a base material, a commercially available silicone hydrogel lens "MyDay (registered trademark)" (manufactured by Cooper Vision, stenfilcon A) containing silicone as a main component was used. Acrylic acid/N,N-dimethylacrylamide copolymer (number ratio of basic group/acidic group 0, molar ratio in copolymerization 1/9, Mw:800,000, manufactured by Osaka Organic Chemical Industry Co., Ltd.) was used as phosphoric acid. An aqueous solution containing 0.2% by mass of the buffer solution was adjusted to pH 3.2 with glycolic acid. The substrate was immersed in the solution and heated in an autoclave at 121°C for 30 minutes. The obtained molded body was immersed and washed in a phosphate buffer for 30 seconds, replaced with a new phosphate buffer, and further heated at 121° C. for 30 minutes in an autoclave. Tables 5 to 8 show the results of evaluation of the obtained molded product by the above method.

Example 35
As a base material, a commercially available silicone hydrogel lens "MyDay (registered trademark)" (manufactured by Cooper Vision, stenfilcon A) containing silicone as a main component was used. Acrylic acid/N,N-dimethylacrylamide copolymer (number ratio of basic group/acidic group 0, molar ratio in copolymerization 1/9, Mw:800,000, manufactured by Osaka Organic Chemical Industry Co., Ltd.) was used as phosphoric acid. An aqueous solution containing 0.2% by mass of the buffer solution was adjusted to pH 3.2 with lactic acid. The substrate was immersed in the solution and heated in an autoclave at 121°C for 30 minutes. The obtained molded body was immersed and washed in a phosphate buffer for 30 seconds, replaced with a new phosphate buffer, and further heated at 121° C. for 30 minutes in an autoclave. Tables 5 to 8 show the results of evaluation of the obtained molded product by the above method.

Example 36
As a base material, a commercially available silicone hydrogel lens "MyDay (registered trademark)" (manufactured by Cooper Vision, stenfilcon A) containing silicone as a main component was used. Acrylic acid/N,N-dimethylacrylamide copolymer (number ratio of basic group/acidic group 0, molar ratio in copolymerization 1/9, Mw:800,000, manufactured by Osaka Organic Chemical Industry Co., Ltd.) was used as phosphoric acid. An aqueous solution containing 0.2% by mass of the buffer solution was adjusted to pH 3.2 with malic acid. The substrate was immersed in the solution and heated in an autoclave at 121°C for 30 minutes. The obtained molded body was immersed and washed in a phosphate buffer for 30 seconds, replaced with a new phosphate buffer, and further heated at 121° C. for 30 minutes in an autoclave. Tables 5 to 8 show the results of evaluation of the obtained molded product by the above method.

[Example 37]
As a base material, a commercially available silicone hydrogel lens "MyDay (registered trademark)" (manufactured by Cooper Vision, stenfilcon A) containing silicone as a main component was used. Acrylic acid/N,N-dimethylacrylamide copolymer (number ratio of basic group/acidic group 0, molar ratio in copolymerization 1/9, Mw:800,000, manufactured by Osaka Organic Chemical Industry Co., Ltd.) was used as phosphoric acid. An aqueous solution containing 0.2% by mass of the buffer solution was adjusted to pH 3.2 with ascorbic acid. The substrate was immersed in the solution and heated in an autoclave at 121°C for 30 minutes. The obtained molded body was immersed and washed in a phosphate buffer for 30 seconds, replaced with a new phosphate buffer, and further heated at 121° C. for 30 minutes in an autoclave. Tables 5 to 8 show the results of evaluation of the obtained molded product by the above method.

[Comparative Example 1]
The molded body obtained in Reference Example 1 was used as the base material. The base material was an acrylic acid/N,N-dimethylacrylamide copolymer (number ratio of basic group/acidic group: 0, molar ratio in copolymerization: 1/9, Mw: 800,000, manufactured by Osaka Organic Chemical Industry Co., Ltd. ) Was immersed in a solution (pH 6.8) containing 0.2% by mass of phosphate buffer solution and heated in an autoclave at 121° C. for 30 minutes. The obtained molded body was washed with a phosphate buffer solution by shaking at 250 rpm for 10 seconds, replaced with a new phosphate buffer solution, and further heated at 121° C. for 30 minutes in an autoclave. Tables 9 to 12 show the results of evaluation of the obtained molded product (no hydrophilic polymer layer was confirmed) by the above method.

[Comparative example 2]
The molded body obtained in Reference Example 1 was used as the base material. The base material was immersed in a solution of a phosphate buffer solution adjusted to pH 2.7 with sulfuric acid, and heated at 121° C. for 30 minutes in an autoclave. The obtained molded body was washed with a phosphate buffer solution by shaking at 250 rpm for 10 seconds, replaced with a new phosphate buffer solution, and further heated at 121° C. for 30 minutes in an autoclave. Tables 9 to 12 show the results of evaluation of the obtained molded product by the above method.

[Comparative Example 3]
The molded body obtained in Reference Example 1 was used as the base material. The base material was an acrylic acid/N,N-dimethylacrylamide copolymer (number ratio of basic group/acidic group: 0, molar ratio in copolymerization: 1/9, Mw: 800,000, manufactured by Osaka Organic Chemical Industry Co., Ltd. ) Was immersed in a solution (pH 6.8) containing 0.2% by mass of phosphate buffer at room temperature (23° C.) and left overnight. The obtained molded body was washed with a phosphate buffer solution by shaking at 250 rpm for 10 seconds, replaced with a new phosphate buffer solution, and further heated at 121° C. for 30 minutes in an autoclave. Tables 9 to 12 show the results of evaluation of the obtained molded product (no hydrophilic polymer layer was confirmed) by the above method.

[Comparative Example 4]
As a base material, a commercially available hydrogel lens "1day Acuvue (registered trademark)" containing 2-hydroxyethyl methacrylate as a main component (manufactured by Johnson & Johnson, etafilcon A) was used. The base material was an acrylic acid/N,N-dimethylacrylamide copolymer (number ratio of basic group/acidic group: 0, molar ratio in copolymerization: 1/9, Mw: 800,000, manufactured by Osaka Organic Chemical Industry Co., Ltd. ) Was immersed in a solution (pH 6.8) containing 0.2% by mass of phosphate buffer at room temperature (23° C.) and left overnight. The obtained molded body was washed with a phosphate buffer solution by shaking at 250 rpm for 10 seconds, replaced with a new phosphate buffer solution, and further heated at 121° C. for 30 minutes in an autoclave. Tables 9 to 12 show the results of evaluation of the obtained molded product (no hydrophilic polymer layer was confirmed) by the above method.

[Comparative Example 5]
The molded body obtained in Reference Example 1 was used as the base material. The substrate contains 0.1% by mass of polyacrylic acid "Sokalan (registered trademark) PA110S" (number ratio of basic group/acidic group 0, Mw: 250,000, manufactured by BASF) in a phosphate buffer. The solution was immersed in the solution (pH 5.3) and heated at 121° C. for 30 minutes in an autoclave. The obtained molded body was washed with a phosphate buffer solution by shaking at 250 rpm for 10 seconds, replaced with a new phosphate buffer solution, and further heated at 121° C. for 30 minutes in an autoclave. Tables 9 to 12 show the results of evaluation of the obtained molded product (no hydrophilic polymer layer was confirmed) by the above method.

[Comparative Example 6]
The molded body obtained in Reference Example 1 was used as the base material. A solution containing 0.2% by mass of polydimethylacrylamide (basic group/acidic group number ratio 0, Mw: 360,000, manufactured by Osaka Organic Chemical Industry Co., Ltd.) in a phosphate buffer solution was adjusted to pH 2. Adjusted to 5. The substrate was immersed in the solution and heated in an autoclave at 121°C for 30 minutes. The obtained molded body was washed with a phosphate buffer solution by shaking at 250 rpm for 10 seconds, replaced with a new phosphate buffer solution, and further heated at 121° C. for 30 minutes in an autoclave. Tables 9 to 12 show the results of evaluation of the obtained molded product (no hydrophilic polymer layer was confirmed) by the above method.

[Comparative Example 7]
The molded body obtained in Reference Example 1 was used as the base material. A solution containing polyvinylpyrrolidone K-90 (basic group/acidic group number ratio 0, Mw: 360,000, manufactured by Tokyo Kasei Kogyo Co., Ltd.) in a phosphate buffer at 0.2 mass% was adjusted to pH 2 with sulfuric acid. Adjusted to .5. The substrate was immersed in the solution and heated in an autoclave at 121°C for 30 minutes. The obtained molded body was washed with a phosphate buffer solution by shaking at 250 rpm for 10 seconds, replaced with a new phosphate buffer solution, and further heated at 121° C. for 30 minutes in an autoclave. Tables 9 to 12 show the results of evaluation of the obtained molded product (no hydrophilic polymer layer was confirmed) by the above method.

[Comparative Example 8]
The molded body obtained in Reference Example 1 was used as the base material. A solution containing 0.2% by mass of polyethylene glycol 200 (basic group/acidic group number ratio 0, Mw 180 to 200, manufactured by Wako Pure Chemical Industries, Ltd.) in a phosphate buffer solution was adjusted to pH 2.5 with sulfuric acid. It was adjusted. The substrate was immersed in the solution and heated in an autoclave at 121°C for 30 minutes. The obtained molded body was washed with a phosphate buffer solution by shaking at 250 rpm for 10 seconds, replaced with a new phosphate buffer solution, and further heated at 121° C. for 30 minutes in an autoclave. Tables 9 to 12 show the results of evaluation of the obtained molded product (no hydrophilic polymer layer was confirmed) by the above method.

[Comparative Example 9]
The molded body obtained in Reference Example 1 was used as the base material. 0.2 mass of poly-N-vinylacetamide "GE-191-103" (basic group/acidic group number ratio 0, Mw: 1,000,000, Showa Denko KK) was added to a phosphate buffer. % Solution was adjusted to pH 2.5 with sulfuric acid. The substrate was immersed in the solution and heated in an autoclave at 121°C for 30 minutes. The obtained molded body was washed with a phosphate buffer solution by shaking at 250 rpm for 10 seconds, replaced with a new phosphate buffer solution, and further heated at 121° C. for 30 minutes in an autoclave. Tables 9 to 12 show the results of evaluation of the obtained molded product (no hydrophilic polymer layer was confirmed) by the above method.

[Comparative Example 10]
The molded body obtained in Reference Example 1 was used as the base material. In a solution containing 0.1% by mass of polyvinyl alcohol (basic group/acidic group number ratio 0, Mw: 31,000 to 50,000, manufactured by SIGMA-ALDRICH) in a phosphate buffer. However, the solubility of polyvinyl alcohol was poor and precipitation occurred in the solution, so that coating could not be carried out.

[Comparative Example 11]
The molded body obtained in Reference Example 1 was used as the base material. A solution containing 0.2% by mass of "methylcellulose 400" (basic group/acidic group number ratio 0, Mw: 84,000, manufactured by Wako Pure Chemical Industries, Ltd.) in a phosphate buffer solution was adjusted to pH 2 with sulfuric acid. Adjusted to .5. The substrate was immersed in the solution and heated in an autoclave at 121°C for 30 minutes. The obtained molded body was washed with a phosphate buffer solution by shaking at 250 rpm for 10 seconds, replaced with a new phosphate buffer solution, and further heated at 121° C. for 30 minutes in an autoclave. Tables 9 to 12 show the results of evaluation of the obtained molded product (no hydrophilic polymer layer was confirmed) by the above method.

[Comparative Example 12]
The molded body obtained in Reference Example 1 was used as the base material. A solution containing 0.2% by mass of poloxamer 407 (basic group/acidic group number ratio 0, Mw: 1,1500, manufactured by BASF) in a phosphate buffer was adjusted to pH 2.5 with sulfuric acid. The substrate was immersed in the solution and heated in an autoclave at 121°C for 30 minutes. The obtained molded body was washed with a phosphate buffer solution by shaking at 250 rpm for 10 seconds, replaced with a new phosphate buffer solution, and further heated at 121° C. for 30 minutes in an autoclave. Tables 9 to 12 show the results of evaluation of the obtained molded product (no hydrophilic polymer layer was confirmed) by the above method.

[Comparative Example 13]
The molded body obtained in Reference Example 1 was used as the base material. A solution containing 0.2% by mass of sodium alginate (basic group/acidic group number ratio 0, manufactured by Showa Kagaku Co., Ltd.) in a phosphate buffer was adjusted to pH 2.5 with sulfuric acid. The substrate was immersed in the solution and heated in an autoclave at 121°C for 30 minutes. The obtained molded body was washed with a phosphate buffer solution by shaking at 250 rpm for 10 seconds, replaced with a new phosphate buffer solution, and further heated at 121° C. for 30 minutes in an autoclave. Tables 9 to 12 show the results of evaluation of the obtained molded product (no hydrophilic polymer layer was confirmed) by the above method.

[Comparative Example 14]
The molded body obtained in Reference Example 1 was used as the base material. The base material was made to contain poly-2-acrylamido-2-methylpropanesulfonic acid (basic group/acidic group number ratio 0, Mw: 200,000, self-made) in a phosphate buffer solution in an amount of 0.05% by mass. It was immersed in the solution (pH 6.8) and heated at 121° C. for 30 minutes in an autoclave. The obtained molded body was washed with a phosphate buffer solution by shaking at 250 rpm for 10 seconds, replaced with a new phosphate buffer solution, and further heated at 121° C. for 30 minutes in an autoclave. Tables 9 to 12 show the results of evaluation of the obtained molded product (no hydrophilic polymer layer was confirmed) by the above method.

[Comparative Example 15]
The molded body obtained in Reference Example 1 was used as the base material. As a base material, poly-2-acrylamido-2-methylpropanesulfonic acid/N,N-dimethylacrylamide copolymer (number ratio of basic group/acidic group 0, molar ratio in copolymerization 1/9, Mw:200 , 1,000, self-produced) was immersed in a solution (pH 6.8) containing 0.05% by mass in a phosphate buffer, and heated in an autoclave at 121° C. for 30 minutes. The obtained molded body was washed with a phosphate buffer solution by shaking at 250 rpm for 10 seconds, replaced with a new phosphate buffer solution, and further heated at 121° C. for 30 minutes in an autoclave. Tables 9 to 12 show the results of evaluation of the obtained molded product (no hydrophilic polymer layer was confirmed) by the above method.

[Comparative Example 16]
The molded body obtained in Reference Example 1 was used as the base material. Polyvinyl acetate/polyvinylpyrrolidone copolymer "PVA-6450" (basic group/acidic group number ratio 0, Mw: 50,000, manufactured by Osaka Organic Chemical Industry Co., Ltd.) was added to 0.2 in a phosphate buffer solution. The solution containing mass% was adjusted to pH 2.5 with sulfuric acid. The substrate was immersed in the solution and heated in an autoclave at 121°C for 30 minutes. The obtained molded body was washed with a phosphate buffer solution by shaking at 250 rpm for 10 seconds, replaced with a new phosphate buffer solution, and further heated at 121° C. for 30 minutes in an autoclave. Tables 9 to 12 show the results of evaluation of the obtained molded product (no hydrophilic polymer layer was confirmed) by the above method.

[Comparative Example 17]
As a base material, a commercially available hydrogel lens "1day Acuvue (registered trademark)" containing 2-hydroxyethyl methacrylate as a main component (manufactured by Johnson & Johnson, etafilcon A) was used. Polyvinyl acetate/polyvinylpyrrolidone copolymer "PVA-6450" (basic group/acidic group number ratio 0, Mw: 50,000, manufactured by Osaka Organic Chemical Industry Co., Ltd.) was added to 0.2 in a phosphate buffer solution. The solution containing mass% was adjusted to pH 2.5 with sulfuric acid. The substrate was immersed in the solution and heated in an autoclave at 121°C for 30 minutes. The obtained molded body was washed with a phosphate buffer solution by shaking at 250 rpm for 10 seconds, replaced with a new phosphate buffer solution, and further heated at 121° C. for 30 minutes in an autoclave. Tables 9 to 12 show the results of evaluation of the obtained molded product (no hydrophilic polymer layer was confirmed) by the above method.

[Comparative Example 18]
As the base material, a commercially available silicone hydrogel lens “1day Acuvue Trueye (registered trademark)” (manufactured by Johnson & Johnson, narafilcon A) containing polyvinylpyrrolidone and silicone as main components was used. 0.2% of polyvinyl acetate/polyvinylpyrrolidone copolymer “PVA-6450” (basic group/acidic group number ratio 0, Mw: 50,000, manufactured by Osaka Organic Chemical Industry Co., Ltd.) in a phosphate buffer solution The solution containing mass% was adjusted to pH 2.5 with sulfuric acid. The substrate was immersed in the solution and heated in an autoclave at 121°C for 30 minutes. The obtained molded body was washed with a phosphate buffer solution by shaking at 250 rpm for 10 seconds, replaced with a new phosphate buffer solution, and further heated at 121° C. for 30 minutes in an autoclave. Tables 9 to 12 show the results of evaluation of the obtained molded product (no hydrophilic polymer layer was confirmed) by the above method.

[Comparative Example 19]
As a base material, a commercially available hydrogel lens "1day Acuvue (registered trademark)" containing 2-hydroxyethyl methacrylate as a main component (manufactured by Johnson & Johnson, etafilcon A) was used. 0.2 mass of poly-N-vinylacetamide "GE-191-103" (basic group/acidic group number ratio 0, Mw: 1,000,000, Showa Denko KK) was added to a phosphate buffer. % Solution was adjusted to pH 2.5 with sulfuric acid. The substrate was immersed in the solution and heated in an autoclave at 121°C for 30 minutes. The obtained molded body was washed with a phosphate buffer solution by shaking at 250 rpm for 10 seconds, replaced with a new phosphate buffer solution, and further heated at 121° C. for 30 minutes in an autoclave. Tables 9 to 12 show the results of evaluation of the obtained molded product (no hydrophilic polymer layer was confirmed) by the above method.

[Comparative Example 20]
A commercially available silicone hydrogel lens "1day Acuvue TruEye (registered trademark)" (manufactured by Johnson & Johnson, narafilcon A) containing polyvinylpyrrolidone and silicone as main components was used as a base material. 0.2 mass of poly-N-vinylacetamide "GE-191-103" (basic group/acidic group number ratio 0, Mw: 1,000,000, Showa Denko KK) was added to a phosphate buffer. % Solution was adjusted to pH 2.5 with sulfuric acid. The substrate was immersed in the solution and heated in an autoclave at 121°C for 30 minutes. The obtained molded body was washed with a phosphate buffer solution by shaking at 250 rpm for 10 seconds, replaced with a new phosphate buffer solution, and further heated at 121° C. for 30 minutes in an autoclave. Tables 9 to 12 show the results of evaluation of the obtained molded product (no hydrophilic polymer layer was confirmed) by the above method.

[Comparative Example 21]
As a base material, a commercially available hydrogel lens "1day Acuvue (registered trademark)" containing 2-hydroxyethyl methacrylate as a main component (manufactured by Johnson & Johnson, etafilcon A) was used. A solution containing 0.2% by mass of sodium alginate (basic group/acidic group number ratio 0, manufactured by Showa Kagaku Co., Ltd.) in a phosphate buffer was adjusted to pH 2.5 with sulfuric acid. The substrate was immersed in the solution and heated in an autoclave at 121°C for 30 minutes. The obtained molded body was washed with a phosphate buffer solution by shaking at 250 rpm for 10 seconds, replaced with a new phosphate buffer solution, and further heated at 121° C. for 30 minutes in an autoclave. Tables 9 to 12 show the results of evaluation of the obtained molded product (no hydrophilic polymer layer was confirmed) by the above method.

[Comparative Example 22]
A commercially available silicone hydrogel lens "1day Acuvue TruEye (registered trademark)" (manufactured by Johnson & Johnson, narafilcon A) containing polyvinylpyrrolidone and silicone as main components was used as a base material. A solution containing 0.2% by mass of sodium alginate (basic group/acidic group number ratio 0, manufactured by Showa Kagaku Co., Ltd.) in a phosphate buffer was adjusted to pH 2.5 with sulfuric acid. The substrate was immersed in the solution and heated in an autoclave at 121°C for 30 minutes. The obtained molded body was washed with a phosphate buffer solution by shaking at 250 rpm for 10 seconds, replaced with a new phosphate buffer solution, and further heated at 121° C. for 30 minutes in an autoclave. Tables 13 to 16 show the results of evaluation of the obtained molded product (no hydrophilic polymer layer was confirmed) by the above method.

[Comparative Example 23]
As a base material, a commercially available hydrogel lens "1day Acuvue (registered trademark)" containing 2-hydroxyethyl methacrylate as a main component (manufactured by Johnson & Johnson, etafilcon A) was used. A solution containing 0.2% by mass of poloxamer 407 (basic group/acidic group number ratio 0, Mw: 11,500, manufactured by BASF) in a phosphate buffer was adjusted to pH 2.5 with sulfuric acid. The substrate was immersed in the solution and heated in an autoclave at 121°C for 30 minutes. The obtained molded body was washed with a phosphate buffer solution by shaking at 250 rpm for 10 seconds, replaced with a new phosphate buffer solution, and further heated at 121° C. for 30 minutes in an autoclave. Tables 13 to 16 show the results of evaluation of the obtained molded product (no hydrophilic polymer layer was confirmed) by the above method.

[Comparative Example 24]
A commercially available silicone hydrogel lens "1day Acuvue TruEye (registered trademark)" (manufactured by Johnson & Johnson, narafilcon A) containing polyvinylpyrrolidone and silicone as main components was used as a base material. A solution containing 0.2% by mass of poloxamer 407 (basic group/acidic group number ratio 0, Mw: 11,500, manufactured by BASF Japan Ltd.) in a phosphate buffer was adjusted to pH 2.5 with sulfuric acid. .. The substrate was immersed in the solution and heated in an autoclave at 121°C for 30 minutes. The obtained molded body was washed with a phosphate buffer solution by shaking at 250 rpm for 10 seconds, replaced with a new phosphate buffer solution, and further heated at 121° C. for 30 minutes in an autoclave. Tables 13 to 16 show the results of evaluation of the obtained molded product (no hydrophilic polymer layer was confirmed) by the above method.

[Comparative Example 25]
As a base material, a commercially available hydrogel lens "1day Acuvue (registered trademark)" containing 2-hydroxyethyl methacrylate as a main component (manufactured by Johnson & Johnson, etafilcon A) was used. The base material was made to contain poly-2-acrylamido-2-methylpropanesulfonic acid (basic group/acidic group number ratio 0, Mw: 200,000, self-made) in a phosphate buffer solution in an amount of 0.05% by mass. It was immersed in the solution (pH 6.8) and heated at 121° C. for 30 minutes in an autoclave. The obtained molded body was washed with a phosphate buffer solution by shaking at 250 rpm for 10 seconds, replaced with a new phosphate buffer solution, and further heated at 121° C. for 30 minutes in an autoclave. Tables 13 to 16 show the results of evaluation of the obtained molded product (no hydrophilic polymer layer was confirmed) by the above method.

[Comparative Example 26]
A commercially available silicone hydrogel lens "1day Acuvue TruEye (registered trademark)" (manufactured by Johnson & Johnson, narafilcon A) containing polyvinylpyrrolidone and silicone as main components was used as a base material. The base material was made to contain poly-2-acrylamido-2-methylpropanesulfonic acid (basic group/acidic group number ratio 0, Mw: 200,000, self-made) in a phosphate buffer solution in an amount of 0.05% by mass. It was immersed in the solution (pH 6.8) and heated at 121° C. for 30 minutes in an autoclave. The obtained molded body was washed with a phosphate buffer solution by shaking at 250 rpm for 10 seconds, replaced with a new phosphate buffer solution, and further heated at 121° C. for 30 minutes in an autoclave. Tables 13 to 16 show the results of evaluation of the obtained molded product (no hydrophilic polymer layer was confirmed) by the above method.

[Comparative Example 27]
As a base material, a commercially available hydrogel lens "1day Acuvue (registered trademark)" containing 2-hydroxyethyl methacrylate as a main component (manufactured by Johnson & Johnson, etafilcon A) was used. As a base material, poly-2-acrylamido-2-methylpropanesulfonic acid/N,N-dimethylacrylamide copolymer (number ratio of basic group/acidic group 0, molar ratio in copolymerization 1/9, Mw:200 , 1,000, self-produced) was immersed in a solution (pH 6.8) containing 0.05% by mass in a phosphate buffer, and heated in an autoclave at 121° C. for 30 minutes. The obtained molded body was washed with a phosphate buffer solution by shaking at 250 rpm for 10 seconds, replaced with a new phosphate buffer solution, and further heated at 121° C. for 30 minutes in an autoclave. Tables 13 to 16 show the results of evaluation of the obtained molded product (no hydrophilic polymer layer was confirmed) by the above method.

[Comparative Example 28]
A commercially available silicone hydrogel lens "1day Acuvue TruEye (registered trademark)" (manufactured by Johnson & Johnson, narafilcon A) containing polyvinylpyrrolidone and silicone as main components was used as a base material. As a base material, poly-2-acrylamido-2-methylpropanesulfonic acid/N,N-dimethylacrylamide copolymer (number ratio of basic group/acidic group 0, molar ratio in copolymerization 1/9, Mw:200 , 1,000, self-produced) was immersed in a solution (pH 6.8) containing 0.05% by mass in a phosphate buffer, and heated in an autoclave at 121° C. for 30 minutes. The obtained molded body was washed with a phosphate buffer solution by shaking at 250 rpm for 10 seconds, replaced with a new phosphate buffer solution, and further heated at 121° C. for 30 minutes in an autoclave. Tables 13 to 16 show the results of evaluation of the obtained molded product (no hydrophilic polymer layer was confirmed) by the above method.

[Comparative Example 29]
The molded body obtained in Reference Example 1 was used as the base material. Acrylic acid/vinylpyrrolidone copolymer (number ratio of basic group/acidic group 0, molar ratio in copolymerization 1/9, Mw: 400,000, manufactured by Osaka Organic Chemical Industry Co., Ltd.) 0.1% by mass and urea An aqueous solution containing 0.3% by mass of pure water was adjusted to pH 3.8 with sulfuric acid. The substrate was immersed in the solution and heated in an autoclave at 121°C for 30 minutes. The obtained molded body was washed with a phosphate buffer solution by shaking at 250 rpm for 30 seconds, replaced with a new phosphate buffer solution, and further heated at 121° C. for 30 minutes in an autoclave. Tables 13 to 16 show the results of evaluation of the obtained molded product (no hydrophilic polymer layer was confirmed) by the above method.

[Comparative Example 30]
As a base material, a commercially available hydrogel lens "Medalist (registered trademark) One Day Plus" (manufactured by Bausch & Lomb, hilafilcon B) containing 2-hydroxyethyl methacrylate as a main component was used. Acrylic acid/vinylpyrrolidone copolymer (number ratio of basic group/acidic group 0, molar ratio in copolymerization 1/9, Mw: 400,000, manufactured by Osaka Organic Chemical Industry Co., Ltd.) 0.1% by mass and 0 The pH of an aqueous solution of pure water containing 3% by mass urea was adjusted to 3.8 with sulfuric acid. The substrate was immersed in the solution and heated in an autoclave at 121°C for 30 minutes. The obtained molded body was washed with a phosphate buffer solution by shaking at 250 rpm for 30 seconds, replaced with a new phosphate buffer solution, and further heated at 121° C. for 30 minutes in an autoclave. Tables 13 to 16 show the results of evaluation of the obtained molded product (no hydrophilic polymer layer was confirmed) by the above method.

[Comparative Example 31]
A commercially available silicone hydrogel lens "1day Acuvue TruEye (registered trademark)" (manufactured by Johnson & Johnson, narafilcon A) containing polyvinylpyrrolidone and silicone as main components was used as a base material. Acrylic acid/N,N-dimethylacrylamide copolymer (number ratio of basic group/acidic group 0, molar ratio in copolymerization 1/9, Mw:800,000, manufactured by Osaka Organic Chemical Industry Co., Ltd.) 0.2 A pH of an aqueous solution containing pure water containing 0.3% by mass of urea and 0.3% by mass of urea was adjusted to 3.0. The substrate was immersed in the solution and heated in an autoclave at 121°C for 30 minutes. The obtained molded body was washed with a phosphate buffer solution by shaking at 250 rpm for 30 seconds, replaced with a new phosphate buffer solution, and further heated at 121° C. for 30 minutes in an autoclave. Tables 13 to 16 show the results of evaluation of the obtained molded product (no hydrophilic polymer layer was confirmed) by the above method.

[Comparative Example 32]
Tables 13 to 16 show the results of evaluation of the commercially available hydrogel lens "1day Acuvue (registered trademark)" (Etafilcon A manufactured by Johnson & Johnson, Inc.) containing 2-hydroxyethyl methacrylate as a main component by the above method.

[Comparative Example 33]
Tables 13 to 16 show the results of the evaluation of the commercially available silicone hydrogel lens "1day Acuvue TruEye (registered trademark)" (manufactured by Johnson & Johnson, narafilcon A) containing polyvinylpyrrolidone and silicone as the main components by the above method.

[Comparative Example 34]
Tables 13 to 16 show the results of evaluation of the commercially available silicone hydrogel lens "Acuvue Oasys (registered trademark)" (manufactured by Johnson & Johnson, senofilcon A) containing polyvinylpyrrolidone and silicone as main components by the above method.

[Comparative Example 35]
The results of evaluation of the commercially available silicone hydrogel lens “Air Optics EX Aqua (registered trademark)” (lotrafilcon B, manufactured by Nihon Alcon Co., Ltd.) having a lens surface treated with plasma as a main component by the above method are shown in Table 13 to. 16 shows.

[Comparative Example 36]
Evaluation was made on a commercially available hydrogel lens "Proclear One Day" (Cooper Vision, omafilcon A) containing 2-hydroxyethyl methacrylate as a main component, which was copolymerized with an MPC monomer (2-methacryloyloxyethylphosphorylcholine), by the above method The results obtained are shown in Tables 13 to 16.

[Comparative Example 37]
The molded body obtained in Reference Example 1 was used as the base material. The base material was made to contain 1.2% by mass of polyacrylic acid "Sokalan (registered trademark) PA110S" (basic group/acidic group number ratio 0, Mw: 250,000, manufactured by BASF) in pure water. It was immersed in the solution (pH 2.6) at 37° C. for 30 minutes. The obtained molded body was washed in pure water with shaking at 250 rpm for 10 seconds and then replaced with a new phosphate buffer solution. Tables 13 to 16 show the results of evaluation of the obtained molded product (no hydrophilic polymer layer was confirmed) by the above method.

[Comparative Example 38]
As a base material, a commercially available hydrogel lens "1day Acuvue (registered trademark)" containing 2-hydroxyethyl methacrylate as a main component (manufactured by Johnson & Johnson, etafilcon A) was used. The base material was made to contain 1.2% by mass of polyacrylic acid "Sokalan (registered trademark) PA110S" (number ratio of basic group/acidic group: 0, Mw: 250,000, manufactured by BASF Japan Ltd.) in pure water. The solution (pH 2.6) was immersed at 37° C. for 30 minutes. The obtained molded body was washed in pure water with shaking at 250 rpm for 10 seconds and then replaced with a new phosphate buffer solution. Tables 13 to 16 show the results of evaluation of the obtained molded product (no hydrophilic polymer layer was confirmed) by the above method.

[Comparative Example 39]
A commercially available silicone hydrogel lens "1day Acuvue TruEye (registered trademark)" (manufactured by Johnson & Johnson, narafilcon A) containing polyvinylpyrrolidone and silicone as main components was used as a base material. The base material was made to contain 1.2% by mass of polyacrylic acid "Sokalan (registered trademark) PA110S" (basic group/acidic group number ratio 0, Mw: 250,000, manufactured by BASF) in pure water. It was immersed in the solution (pH 2.6) at 37° C. for 30 minutes. The obtained molded body was washed in pure water with shaking at 250 rpm for 10 seconds and then replaced with a new phosphate buffer solution. Tables 13 to 16 show the results of evaluation of the obtained molded product (no hydrophilic polymer layer was confirmed) by the above method.

[Comparative Example 40]
The molded body obtained in Reference Example 1 was used as the base material. The substrate was immersed in an aqueous solution containing hydrochloric acid (pH 3.0) at room temperature for 5 minutes, and then washed by shaking in pure water at 250 rpm for 10 seconds. Then, the base material contained 0.1% by mass of polyacrylic acid "Sokalan (registered trademark) PA110S" (number ratio of basic group/acidic group 0, Mw: 250,000, manufactured by BASF) in pure water. The solution (pH 3.3) was immersed for 5 minutes at room temperature. The obtained molded body was washed in pure water with shaking at 250 rpm for 10 seconds and then replaced with a new phosphate buffer solution. Tables 13 to 16 show the results of evaluation of the obtained molded product (no hydrophilic polymer layer was confirmed) by the above method.

[Comparative Example 41]
As a base material, a commercially available hydrogel lens "1day Acuvue (registered trademark)" containing 2-hydroxyethyl methacrylate as a main component (manufactured by Johnson & Johnson, etafilcon A) was used. The substrate was immersed in an aqueous solution containing hydrochloric acid (pH 3.0) for 5 minutes at room temperature, and then washed by shaking in pure water at 250 rpm for 10 seconds. Then, the base material contained 0.1% by mass of polyacrylic acid "Sokalan (registered trademark) PA110S" (number ratio of basic group/acidic group 0, Mw: 250,000, manufactured by BASF) in pure water. The solution (pH 3.3) was dipped at room temperature for 5 minutes. The obtained molded body was washed in pure water with shaking at 250 rpm for 10 seconds and then replaced with a new phosphate buffer solution. Tables 13 to 16 show the results of evaluation of the obtained molded product (no hydrophilic polymer layer was confirmed) by the above method.

[Comparative Example 42]
A commercially available silicone hydrogel lens "1day Acuvue TruEye (registered trademark)" (manufactured by Johnson & Johnson, narafilcon A) containing polyvinylpyrrolidone and silicone as main components was used as a base material. The substrate was immersed in an aqueous solution containing hydrochloric acid (pH 3.0) for 5 minutes at room temperature, and then washed by shaking in pure water at 250 rpm for 10 seconds. Then, the base material contained 0.1% by mass of polyacrylic acid "Sokalan (registered trademark) PA110S" (number ratio of basic group/acidic group 0, Mw: 250,000, manufactured by BASF) in pure water. The solution (pH 3.3) was dipped at room temperature for 5 minutes. The obtained molded body was washed in pure water with shaking at 250 rpm for 10 seconds and then replaced with a new phosphate buffer solution. Tables 13 to 16 show the results of evaluation of the obtained molded product (no hydrophilic polymer layer was confirmed) by the above method.

[Comparative Example 43]
The molded body obtained in Reference Example 1 was used as the base material. When the base material was put into a solution containing 0.1% by mass of pure water of Chitosan (0.5% in 0.5% Acoustic Acid at 20° C.) (manufactured by TCI), dissolution of Chitosan was observed. The coating was not able to be performed due to poor property and precipitation in the solution.

[Comparative Example 44]
The molded body obtained in Reference Example 1 was used as the base material. As the base material, 0.18 mass% of polyacrylic acid (basic group/acidic group number ratio 0, "Sokalan PA110S", Mw 250,000, manufactured by BASF) and 0.02 mass% of acrylic acid/N,N -Dimethylacrylamide copolymer (copolymerization ratio 1/9, Mw 800,000, manufactured by Osaka Organic Chemical Industry Co., Ltd.) was immersed in a phosphate buffer, and heated at 121°C for 30 minutes in an autoclave. Tables 17 to 20 show the results of evaluation of the obtained molded product (no hydrophilic polymer layer was confirmed) by the above method.

[Comparative Example 45]
A commercially available silicone hydrogel lens "1day Acuvue TruEye (registered trademark)" (manufactured by Johnson & Johnson, narafilcon A) containing polyvinylpyrrolidone and silicone as main components was used as a base material. As the base material, 0.18 mass% of polyacrylic acid (basic group/acidic group number ratio 0, "Sokalan PA110S", Mw 250,000, manufactured by BASF) and 0.02 mass% of acrylic acid/N,N -Dimethyl acrylamide copolymer (basic group/acidic group number ratio 0, copolymerization ratio 1/9, Mw 800,000, manufactured by Osaka Organic Chemical Industry Co., Ltd.) It was heated in an autoclave at 121°C for 30 minutes. Tables 17 to 20 show the results of evaluation of the obtained molded product (no hydrophilic polymer layer was confirmed) by the above method.

[Comparative Example 46]
As a base material, a commercially available hydrogel lens "1day Acuvue (registered trademark)" containing 2-hydroxyethyl methacrylate as a main component (manufactured by Johnson & Johnson, etafilcon A) was used. The base material was 0.18% by mass of polyacrylic acid (basic group/acidic group number ratio 0, "Sokalan PA110S", Mw 250,000, manufactured by BASF) and 0.02% by mass of acrylic acid/N,N. -Dimethyl acrylamide copolymer (basic group/acidic group number ratio 0, copolymerization ratio 1/9, Mw 800,000, manufactured by Osaka Organic Chemical Industry Co., Ltd.) and immersed in a phosphate buffer solution. , 121° C., 30 minutes in an autoclave. Tables 17 to 20 show the results of evaluation of the obtained molded product (no hydrophilic polymer layer was confirmed) by the above method.

[Comparative Example 47]
The molded body obtained in Reference Example 1 was used as the base material. The base material was dissolved in pure water of polyacrylic acid (number ratio of basic group/acidic group 0, "Sokalan PA110S", Mw 250,000, manufactured by BASF) to 1.2% by mass at room temperature. And soaked for 30 minutes. Then, it was lightly rinsed with pure water in a beaker. The molded body was transferred to a beaker containing fresh pure water, and put in an ultrasonic cleaner (30 seconds). Further, it was lightly rinsed in a beaker containing fresh pure water. Then, a solution of polyethyleneimine (basic group/acidic group number ratio 0, Mw 750,000, manufactured by Junsei Chemical Co., Ltd.) in pure water to 1% by mass, acrylic acid/N,N-dimethylacrylamide copolymer (Basic group/acidic group number ratio 0, copolymerization ratio 1/9, Mw 800,000, manufactured by Osaka Organic Chemical Industry Co., Ltd.) was dissolved in pure water to a concentration of 0.1% by mass. Then, the same operation was repeated in this order. After finishing the coating operation, the molded body was immersed in a phosphate buffer solution and heated in an autoclave at 121° C. for 30 minutes. Tables 17 to 20 show the results of evaluation of the obtained molded product (number ratio of basic group/acidic group of hydrophilic polymer layer 0.5) by the above method.

[Comparative Example 48]
A commercially available silicone hydrogel lens "1day Acuvue TruEye (registered trademark)" (manufactured by Johnson & Johnson, narafilcon A) containing polyvinylpyrrolidone and silicone as main components was used as a base material. The base material was immersed for 30 minutes at room temperature in a solution in which polyacrylic acid (“Sokalan PA110S”, Mw 250,000, manufactured by BASF) was dissolved in pure water to make 1.2 mass %. Then, it was lightly rinsed with pure water in a beaker. The molded body was transferred to a beaker containing fresh pure water, and put in an ultrasonic cleaner (30 seconds). Further, it was lightly rinsed in a beaker containing fresh pure water. Then, a solution of polyethyleneimine (Mw 750,000, manufactured by Junsei Chemical Co., Ltd.) in pure water to make it 1% by mass, acrylic acid/N,N-dimethylacrylamide copolymer (copolymerization ratio 1/9, Mw 800, 000, manufactured by Osaka Organic Chemical Industry Co., Ltd.) was dissolved in pure water to make 0.1% by mass, and the same operation was repeated in this order. After finishing the coating operation, the molded body was immersed in a phosphate buffer solution and heated in an autoclave at 121° C. for 30 minutes. Tables 17 to 20 show the results of evaluation of the obtained molded product (number ratio of basic group/acidic group of hydrophilic polymer layer 0.5) by the above method.

[Comparative Example 49]
As a base material, a commercially available hydrogel lens "1day Acuvue (registered trademark)" containing 2-hydroxyethyl methacrylate as a main component (manufactured by Johnson & Johnson, etafilcon A) was used. The base material was immersed for 30 minutes at room temperature in a solution in which polyacrylic acid (“Sokalan PA110S”, Mw 250,000, manufactured by BASF) was dissolved in pure water to make 1.2 mass %. Then, it was lightly rinsed with pure water in a beaker. The molded body was transferred to a beaker containing fresh pure water, and put in an ultrasonic cleaner (30 seconds). Further, it was lightly rinsed in a beaker containing fresh pure water. Then, a solution of polyethyleneimine (Mw 750,000, manufactured by Junsei Chemical Co., Ltd.) in pure water to make it 1% by mass, acrylic acid/N,N-dimethylacrylamide copolymer (copolymerization ratio 1/9, Mw 800, 000, manufactured by Osaka Organic Chemical Industry Co., Ltd.) was dissolved in pure water to make 0.1% by mass, and the same operation was repeated in this order. After the coating operation was completed, the molded body was greatly deformed and could not be used for evaluation without forming the lens shape.

[Comparative Example 50]
A commercially available silicone hydrogel lens "1day Acuvue TruEye (registered trademark)" (manufactured by Johnson & Johnson, narafilcon A) containing polyvinylpyrrolidone and silicone as main components was used as a base material. The base material is an acrylic acid/N,N-dimethylacrylamide copolymer (number ratio of basic group/acidic group is 0, molar ratio in copolymerization is 1/9, Mw: 200,000, manufactured by Osaka Organic Chemical Industry Co., Ltd. Of 0.1% by weight in pure water is immersed in a solution of which the pH is adjusted to 3.5 with sulfuric acid, and ultrasonic cleaning is performed for 2 hours between room temperature and about 40° C. (model US-IR, AS ONE (Made by the company). The obtained molded body was immersed and washed in pure water for 30 seconds, replaced with a new phosphate buffer solution, and further heated at 121° C. for 30 minutes in an autoclave. Tables 17 to 20 show the results of evaluation of the obtained molded product (no hydrophilic polymer layer was confirmed) by the above method.

[Comparative Example 51]
The molded body obtained in Reference Example 1 was used as the base material. The base material is an acrylic acid/N,N-dimethylacrylamide copolymer (number ratio of basic group/acidic group is 0, molar ratio in copolymerization is 1/9, Mw: 200,000, manufactured by Osaka Organic Chemical Industry Co., Ltd. Of 0.1% by weight in pure water is immersed in a solution of which the pH is adjusted to 3.5 with sulfuric acid, and ultrasonic cleaning is performed for 2 hours between room temperature and about 40° C. (model US-IR, AS ONE (Made by the company). The obtained molded body was immersed and washed in pure water for 30 seconds, replaced with a new phosphate buffer solution, and further heated at 121° C. for 30 minutes in an autoclave. Tables 17 to 20 show the results of evaluation of the obtained molded product (no hydrophilic polymer layer was confirmed) by the above method.

[Comparative Example 52]
As a base material, a commercially available hydrogel lens "Proclear One Day" (manufactured by Cooper Vision) having 2-hydroxyethyl methacrylate as a main component, which was copolymerized with an MPC monomer (2-methacryloyloxyethylphosphorylcholine) was used. The base material is an acrylic acid/N,N-dimethylacrylamide copolymer (number ratio of basic group/acidic group is 0, molar ratio in copolymerization is 1/9, Mw: 200,000, manufactured by Osaka Organic Chemical Industry Co., Ltd. Of 0.1% by weight in pure water is immersed in a solution of which the pH is adjusted to 3.5 with sulfuric acid, and ultrasonic cleaning is performed for 2 hours between room temperature and about 40° C. (model US-IR, AS ONE (Made by the company). The obtained molded body was immersed and washed in pure water for 30 seconds, replaced with a new phosphate buffer solution, and further heated at 121° C. for 30 minutes in an autoclave. Tables 17 to 20 show the results of evaluation of the obtained molded product (no hydrophilic polymer layer was confirmed) by the above method.

[Comparative Example 53]
As the base material, a commercially available silicone hydrogel lens "1day Acuvue TruEye (registered trademark)" containing polyvinylpyrrolidone and silicone as main components (manufactured by Johnson & Johnson) was used. The base material was an acrylic acid/N,N-dimethylacrylamide copolymer (number ratio of basic group/acidic group: 0, molar ratio in copolymerization: 1/9, Mw: 200,000, manufactured by Osaka Organic Chemical Industry Co., Ltd. Was immersed in a solution of which the pH was adjusted to 3.5 by sulfuric acid, and heated at 121° C. for 30 minutes in an autoclave. The obtained molded body was immersed in pure water for 30 seconds, washed, replaced with a new phosphate buffer solution, and further heated at 121° C. for 30 minutes in an autoclave. Tables 17 to 20 show the results of evaluation of the obtained molded product (no hydrophilic polymer layer was confirmed) by the above method.

[Comparative Example 54]
The molded body obtained in Reference Example 1 was used as the base material. The base material is an acrylic acid/N,N-dimethylacrylamide copolymer (number ratio of basic group/acidic group is 0, molar ratio in copolymerization is 1/9, Mw: 200,000, manufactured by Osaka Organic Chemical Industry Co., Ltd. Was immersed in a solution of which the pH was adjusted to 3.5 by sulfuric acid, and the mixture was heated at 121° C. for 30 minutes in an autoclave. The obtained molded body was immersed and washed in pure water for 30 seconds, replaced with a new phosphate buffer solution, and further heated at 121° C. for 30 minutes in an autoclave. Tables 17 to 20 show the results of evaluation of the obtained molded product (no hydrophilic polymer layer was confirmed) by the above method.

[Comparative Example 55]
As a base material, a commercially available silicone hydrogel lens "Acuvue Oasis (registered trademark)" (manufactured by Johnson & Johnson) having polyvinylpyrrolidone and silicone as main components was used. Acrylic acid/N,N-dimethylacrylamide copolymer (number ratio of basic group/acidic group 0, molar ratio in copolymerization 1/9, Mw: 800,000, manufactured by Osaka Organic Chemical Industry Co., Ltd.) in pure water The pH of the aqueous solution containing 0.2 mass% was adjusted to 1.9 with sulfuric acid. The substrate was put in the solution and heated in an autoclave at 121°C for 30 minutes. The obtained molded body was washed with a phosphate buffer solution by shaking at 250 rpm for 10 seconds, replaced with a new phosphate buffer solution, and further heated at 121° C. for 30 minutes in an autoclave. Since the polymer layer of the obtained molded body is thick, the refraction of light is disturbed, and when the character on the opposite side of the lens is seen through the lens in the air, the character on the opposite side is blurred and unrecognizable, which is necessary for the lens. The optical performance was remarkably insufficient. Tables 17 to 20 show the results of evaluation of the obtained molded body by the above method.

[Comparative Example 56]
As a base material, a commercially available hydrogel lens "1day Acuvue (registered trademark)" containing 2-hydroxyethyl methacrylate as a main component (manufactured by Johnson & Johnson, etafilcon A) was used. Acrylic acid/N,N-dimethylacrylamide copolymer (number ratio of basic group/acidic group 0, molar ratio in copolymerization 1/9, Mw: 800,000, manufactured by Osaka Organic Chemical Industry Co., Ltd.) in pure water The pH of the aqueous solution containing 0.2 mass% was adjusted to 1.9 with sulfuric acid. The substrate was put in the solution and heated in an autoclave at 121°C for 30 minutes. The obtained molded body was washed with a phosphate buffer solution by shaking at 250 rpm for 10 seconds, replaced with a new phosphate buffer solution, and further heated at 121° C. for 30 minutes in an autoclave. Since the polymer layer of the obtained molded body is thick, the refraction of light is disturbed, and when the character on the opposite side of the lens is seen through the lens in the air, the character on the opposite side is blurred and unrecognizable, which is necessary for the lens. The optical performance was remarkably insufficient. Tables 17 to 20 show the results of evaluation of the obtained molded body by the above method.

[Comparative Example 57]
The molded body obtained in Reference Example 1 was used as the base material. Acrylic acid/N,N-dimethylacrylamide copolymer (number ratio of basic group/acidic group 0, molar ratio in copolymerization 1/9, Mw: 800,000, manufactured by Osaka Organic Chemical Industry Co., Ltd.) in pure water The pH of the aqueous solution containing 0.2 mass% was adjusted to 1.9 with sulfuric acid. The substrate was put in the solution and heated in an autoclave at 121°C for 30 minutes. The obtained molded body was washed with a phosphate buffer solution by shaking at 250 rpm for 10 seconds, replaced with a new phosphate buffer solution, and further heated at 121° C. for 30 minutes in an autoclave. Since the polymer layer of the obtained molded body is thick, the refraction of light is disturbed, and when the character on the opposite side of the lens is seen through the lens in the air, the character on the opposite side is blurred and unrecognizable, which is necessary for the lens. The optical performance was remarkably insufficient. Tables 17 to 20 show the results of evaluation of the obtained molded body by the above method.

[Comparative Example 58]
As a base material, a commercially available silicone hydrogel lens "MyDay (registered trademark)" (manufactured by Cooper Vision, stenfilcon A) containing silicone as a main component was used. Acrylic acid/acrylamide copolymer (number ratio of basic group/acidic group: 0, molar ratio in copolymerization: 6/4, Mw: 200,000, self-made) was used as a base material in a phosphate buffer solution at a concentration of 0.19. When an attempt was made to immerse the mass% aqueous solution in a solution adjusted to pH 3.2 with citric acid, white precipitation occurred in the solution adjusted to pH 3.2, and coating could not be performed.

[Comparative Example 59]
As a base material, a commercially available silicone hydrogel lens "MyDay (registered trademark)" (manufactured by Cooper Vision, stenfilcon A) containing silicone as a main component was used. 0.19% by mass of acrylic acid/acrylamide copolymer (number ratio of basic group/acidic group 0, molar ratio in copolymerization 7/93, Mw: 200,000, self-made) was contained in a phosphate buffer solution. The aqueous solution was adjusted to pH 3.2 with citric acid. The substrate was immersed in the solution and heated in an autoclave at 121°C for 30 minutes. The obtained molded body was immersed and washed in a phosphate buffer for 30 seconds, replaced with a new phosphate buffer, and further heated at 121° C. for 30 minutes in an autoclave. Tables 17 to 20 show the results of evaluation of the obtained molded product (no hydrophilic polymer layer was confirmed) by the above method.

[Comparative Example 60]
As a base material, a commercially available silicone hydrogel lens "MyDay (registered trademark)" (manufactured by Cooper Vision, stenfilcon A) containing silicone as a main component was used. 0.19% by mass of acrylic acid/acrylamide copolymer (number ratio of basic group/acidic group 0, molar ratio in copolymerization 1/9, Mw: 200,000, self-made) was contained in a phosphate buffer. The aqueous solution was adjusted to pH 3.2 with citric acid. The substrate was immersed in the solution and heated in an autoclave at 121°C for 30 minutes. The obtained molded body was immersed and washed in a phosphate buffer for 30 seconds, replaced with a new phosphate buffer, and further heated at 121° C. for 30 minutes in an autoclave. Tables 17 to 20 show the results of evaluation of the obtained molded product (no hydrophilic polymer layer was confirmed) by the above method.

[Comparative Example 61]
As a base material, a commercially available silicone hydrogel lens "MyDay (registered trademark)" (manufactured by Cooper Vision, stenfilcon A) containing silicone as a main component was used. 0.19 mass% of acrylic acid/acrylamide copolymer (number ratio of basic group/acidic group 0, molar ratio in copolymerization 3/7, Mw: 200,000, self-produced) was contained in a phosphate buffer. The aqueous solution was adjusted to pH 3.2 with citric acid. The substrate was immersed in the solution and heated in an autoclave at 121°C for 30 minutes. The obtained molded body was immersed and washed in a phosphate buffer for 30 seconds, replaced with a new phosphate buffer, and further heated at 121° C. for 30 minutes in an autoclave. Tables 17 to 20 show the results of evaluation of the obtained molded product (no hydrophilic polymer layer was confirmed) by the above method.

[Comparative Example 62]
Tables 17 to 20 show the results of evaluation of the commercially available silicone hydrogel lens "MyDay (registered trademark)" (Stenfilcon A manufactured by Cooper Vision Co., Ltd.) containing silicone as a main component by the above method.

Claims (16)

A medical device comprising a base material and a hydrophilic polymer layer on at least a part of the base material, and satisfying the following conditions (a) to (d):
(A) the polymer constituting the hydrophilic polymer layer is a hydrophilic polymer containing an acidic group;
(B) the thickness of the hydrophilic polymer layer is 1 nm or more and less than 100 nm;
(C) The number ratio of basic groups/acidic groups of the hydrophilic polymer layer is 0.2 or less;
(D) The liquid film retention time after 40 minutes of immersion in a phosphate buffer solution and ultrasonic cleaning is 15 seconds or more. The medical device according to claim 1, wherein at least a part of the hydrophilic polymer layer exists in a state of being mixed with the base material. The medical device according to claim 1, wherein the hydrophilic polymer further has an amide group. The medical device according to any one of claims 1 to 3, wherein the substrate contains one or more kinds of materials selected from hydrogels, silicone hydrogels, low hydrous soft materials, and low hydrous hard materials. The hydrogel is selected tefilcon, tetrafilcon, helfilcon, mafilcon, polymacon, hioxifilcon, alfafilcon, omafilcon, hioxifilcon, nelfilcon, nesofilcon, hilafilcon, acofilcon, deltafilcon, etafilcon, focofilcon, ocufilcon, phemfilcon, methafilcon, and from the group consisting of vilfilcon The medical device according to claim 4, which is a hydrogel. The silicone hydrogels, lotrafilcon, galyfilcon, narafilcon, senofilcon, the group consisting of comfilcon, enfilcon, balafilcon, efrofilcon, fanfilcon, somofilcon, samfilcon, olifilcon, asmofilcon, formofilcon, stenfilcon, abafilcon, mangofilcon, riofilcon, sifilcon, larafilcon, and from delefilcon The medical device according to claim 4, which is a silicone hydrogel selected from the group consisting of: The medical device according to claim 4, wherein the low hydrous soft material is a material containing silicon atoms. The medical device according to claim 4, wherein the low hydrous hard material is a material containing silicon atoms. The medical device according to claim 4 or 8, wherein the low hydrous hard material is polymethylmethacrylate. The medical device according to claim 4, 8, or 9, wherein the low hydrous hard material is a material selected from the group consisting of neofocon, pasifocon, telefocon, silafocon, paflufocon, petrafocon, and fluorofocon. Ophthalmic lens, skin coating, wound coating, skin protective material, drug carrier for skin, infusion tube, gas transport tube, drainage tube, blood circuit, coating tube, catheter, stent, sheath bio The medical device according to any one of claims 1 to 10, which is a sensor chip or a covering material for an endoscope. The medical device according to claim 11, which is a contact lens satisfying the following (e).
(E) The average thickness of the hydrophilic polymer layer on the front curve surface and the average thickness of the hydrophilic polymer layer on the base curve surface have a thickness difference of more than 20%. The medical device according to claim 11 or 12, wherein the medical device is a contact lens. A method of manufacturing the medical device according to any one of claims 1 to 13,
Placing the substrate in a solution having an initial pH of 2.0 or more and 6.0 or less and heating the solution;
The method for producing a medical device, wherein the solution contains the hydrophilic polymer and an acid. The acid is an organic acid containing at least one selected from acetic acid, citric acid, formic acid, ascorbic acid, trifluoromethanesulfonic acid, methanesulfonic acid, propionic acid, butyric acid, glycolic acid, lactic acid and malic acid. 15. The method for manufacturing the medical device according to 14. The method for manufacturing a medical device according to claim 14, wherein the step of heating the solution is performed using an autoclave.